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TW201350479A - TrK inhibitor compound - Google Patents

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TW201350479A
TW201350479A TW102114781A TW102114781A TW201350479A TW 201350479 A TW201350479 A TW 201350479A TW 102114781 A TW102114781 A TW 102114781A TW 102114781 A TW102114781 A TW 102114781A TW 201350479 A TW201350479 A TW 201350479A
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alkyl
phenoxy
urea
thiazol
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TW102114781A
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Jun Takeuchi
Masahiro Ikura
Masato Higashino
Maki Iwahashi
Kazuya Hashimura
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Ono Pharmaceutical Co
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Abstract

The present invention provides a medicament containing a compound having a Trk inhibitor activity as an active ingredient for prevention and/or treatment of the diseases such as pain, pruritus, lower urinary tract disorders, asthma, allergic rhinitis, inflammatory bowel disease, or Chagas disease. The present invention provides a compound represented by formula (I), a salt thereof, a N-oxide form thereof, a solvate thereof, or their pro-drugs as a pharmaceutical ingredients having Trk inhibitor activity for prevention and/or treatment of the diseases such as pain, pruritus, lower urinary tract disorders, asthma, allergic rhinitis, inflammatory bowel disease, or Chagas disease. (Wherein all symbols represent the same meaning as the symbols described in the specification.)

Description

Trk阻害化合物 Trk inhibitor compound

本發明係有關Trk阻害化合物或其鹽、及將該等作為有效成分含有之醫藥。詳言之，係有關含有通式(I)表示之Trk阻害化合物、其鹽、其N-氧化物、其溶劑化物或該等之前驅藥(以下，將該等總稱為本發明化合物)。 The present invention relates to a Trk-inhibiting compound or a salt thereof, and a medicine contained as such an active ingredient. More specifically, it relates to a Trk-inhibiting compound represented by the formula (I), a salt thereof, an N-oxide thereof, a solvate thereof or the like (hereinafter, collectively referred to as a compound of the present invention).

(式中，所有符號與後述同意義)、及將該等作為有效成分含有之醫藥。 (All symbols in the formulae have the same meanings as described later), and the medicines contained as the active ingredients.

原肌球蛋白受體激酶(Tropomiosin-receptor kinase)(以下，簡稱為Trk)家族屬於受體型酪胺酸激酶，並分類為神經成長因子(以下，簡稱為NGF)之高親和性受體之TrkA、源自腦之營養因子(BDNF)及神經營養素(以下，簡稱為NT)-4/5之高親和性受體之TrkB、及NT-3高親和性受體之TrkC。任何一種Trk受體都於神經組織中高度地被發現，並參予神經細胞分化或機能維持(參照非專利文獻1)。另一方面，已知若經由NGF將末梢神經之TrkA 活化，則會引起痛覺過敏(參照非專利文獻2)，根據使用抗NGF抗體之臨床及非臨床試驗結果或使用低分子Trk阻害劑之非臨床試驗結果，有TrkA參予變形性關節炎、慢性腰痛症、風濕性關節炎、骨折、間質性膀胱炎及慢性胰臟炎等伴隨之侵害接受性疼痛、神經障害性疼痛及合併雙方疼痛之癌症性疼痛等疼痛之報告(參照非專利文獻3至10)。另，有Trk受體於神經芽腫、前列腺癌及胰臟癌等癌細胞、肥大細胞或嗜酸性球等炎症細胞、T細胞或B細胞等免疫細胞及角質細胞等亦被發現，有可能參予癌細胞増殖、遊走及轉移、潰瘍性大腸炎及克隆氏症(Crohn's disease)等發炎性疾病、氣喘、鼻炎、異位性皮膚炎等過敏性疾病、及乾癬等疾病之報告(參照非專利文獻11至15)。因此，具有Trk阻害活性之化合物可能可應用於侵害接受性疼痛、神經障害性疼痛及合併雙方疼痛之疼痛、癌症、發炎性疾病、過敏性疾病及乾癬等之治療。 Tropomyosin receptor kinase (T ropomiosin -receptor kinase) (hereinafter referred to as Trk) family of receptor tyrosine kinases belong to, and are classified as nerve growth factor (hereinafter referred to as NGF) high affinity receptor TrkA, brain-derived trophic factor (BDNF) and neurotrophin (hereinafter abbreviated as NT)-4/5 high affinity receptor TrkB, and NT-3 high affinity receptor TrkC. Any of the Trk receptors is highly found in nerve tissues and participates in nerve cell differentiation or function maintenance (see Non-Patent Document 1). On the other hand, it is known that if TrkA of peripheral nerves is activated by NGF, hyperalgesia is caused (refer to Non-Patent Document 2), non-clinical according to clinical and non-clinical test results using anti-NGF antibodies or low molecular weight Trk inhibitors. The results of the test, TrkA involved in deformed arthritis, chronic low back pain, rheumatoid arthritis, fractures, interstitial cystitis and chronic pancreatitis, accompanied by invasive pain, neuropathic pain and combined pain Report of pain such as cancer pain (see Non-Patent Documents 3 to 10). In addition, Trk receptors are also found in cancer cells such as neuroblasts, prostate cancer, and pancreatic cancer, inflammatory cells such as mast cells or eosinophils, immune cells such as T cells or B cells, and keratinocytes. Reports on inflammatory diseases such as cancer cell migration, migration and metastasis, ulcerative colitis and Crohn's disease , allergic diseases such as asthma, rhinitis, atopic dermatitis, and diseases such as dryness (see Non-patent) Documents 11 to 15). Therefore, a compound having Trk inhibitory activity may be applied to treatments for receiving pain, neuropathic pain, pain combined with pain on both sides, cancer, inflammatory disease, allergic disease, and cognac.

由此來看，只要可創製阻害Trk之藥劑，Trk阻害劑即可期待可能成為至今未有之新型疼痛等之預防劑及/或治療劑。 From this point of view, as long as the agent for inhibiting Trk can be created, the Trk inhibitor can be expected to be a preventive and/or therapeutic agent for new types of pain and the like which have not been hitherto.

另一方面，於專利文獻1中記載，經由酪胺酸激酶調節，之用於處置或預防人類或其他哺乳類疾病之方法，包含於需要之人類或其他哺乳類投予下述式(Ia)之化合物、其鹽、其異構體或其化合物之前驅藥之方法。 On the other hand, Patent Document 1 discloses a method for treating or preventing a human or other mammalian disease, which is regulated by tyrosine kinase, and which comprises administering a compound of the following formula (Ia) to a human or other mammal in need thereof. A method in which a salt, an isomer thereof or a compound thereof is pre-drug-driven.

通式(Ia)為 General formula (Ia) is

(式中，Aa為選自下述(i)至(iii)等群；(i)可經1至3個任意獨立選自Ra1、ORa1、鹵素原子等群之取代基取代之苯基；(ii)可經1至3個任意獨立選自Ra1、ORa1、鹵素原子等群之取代基取代之萘基；(iii)可經1至3個任意獨立選自Ra1、ORa1、鹵素原子等群之取代基取代的，具有1至3個獨立選自氧原子、氮原子及硫原子所成群組之雜原子之5及6員單環雜芳基；Ba為選自下述(i)至(iii)等群；(i)可經1至3個任意獨立選自-La-Ma、C1-C5直鏈或支鏈烷基、鹵素原子等群之取代基取代之苯基；(ii)可經1至3個任意獨立選自-La-Ma、C1-C5直鏈或支鏈烷基、鹵素原子等群之取代基取代之萘基；(iii)可經1至3個任意獨立選自-La-Ma、C1-C5直鎖或支鏈烷基、鹵素原子等群之取代基取代的，具有1至3個獨立選自由氧原子、氮原子及硫原子所成群組之雜原子之5及6員單環雜芳基；La為選自-(CH2)ma-O-(CH2)1a-、-(CH2)ma-C(O)-(CH2)1a-等群，此處，變數ma及1a為獨立選自0至4之整數；Ma為選自下述(i)至(iii)等群；(i)可經1至3個任意獨立選自Ra1、ORa1、鹵素原子等群之取代基取代之苯基；(ii)可經1至3個任意獨立選自Ra1、ORa1、鹵素原子等群之取代基取代之萘基；(iii)可經1至3個任意獨立選自Ra1、ORa1、鹵素原子等群之 取代基取代，具有1至3個獨立選自由氧原子、氮原子及硫原子所成群組之雜原子之5及6員單環雜芳基；此處，Ra1為獨立選自由(a)至(f)所成群組，(a)氫原子、(b)C1-C6烷基、(c)苯基、(d)具有1至4個選自由氧原子、氮原子及硫原子所成群組之雜原子之5至6員單環雜芳基或8至10員二環雜芳基、(e)C1-C3烷基-苯基、及(f)具有1至4個選自由氧原子、氮原子及硫原子所成群組之雜原子之烷基-雜芳基；Ra1不為氫原子時，可經1至3個任意獨立選自由C1-C5直鏈、支鏈或環狀烷基、C1-C3烷氧基、羥基、胺基、C1-C3烷基胺基、C2-C6二烷基胺基、鹵素原子、氰基及硝基所成群組之取代基取代。(摘錄一部分基之定義。))。 (wherein Aa is a group selected from the group consisting of (i) to (iii) below; (i) a phenyl group which may be substituted with 1 to 3 substituents independently selected from the group consisting of Ra 1 , ORa 1 , and a halogen atom; (ii) a naphthyl group which may be substituted with 1 to 3 substituents independently selected from the group consisting of Ra 1 , ORa 1 , a halogen atom, etc.; (iii) may be independently selected from 1 to 3 independently selected from Ra 1 , ORa 1 a 5- and 6-membered monocyclic heteroaryl group having 1 to 3 hetero atoms independently selected from the group consisting of an oxygen atom, a nitrogen atom and a sulfur atom; and Ba is selected from the group consisting of a substituent of a group such as a halogen atom; a group such as (i) to (iii); (i) may be substituted with 1 to 3 substituents independently selected from the group consisting of -La-Ma, C 1 -C 5 linear or branched alkyl groups, halogen atoms, and the like a phenyl group; (ii) a naphthyl group which may be substituted with 1 to 3 substituents independently selected from the group consisting of -La-Ma, C 1 -C 5 linear or branched alkyl groups, halogen atoms, etc.; It may be substituted by 1 to 3 substituents independently selected from the group consisting of -La-Ma, C 1 -C 5 straight or branched alkyl, halogen atom, etc., having 1 to 3 independently selected from oxygen atom, nitrogen 5 and 6 membered monocyclic heteroaryl groups of a hetero atom in a group of atoms and sulfur atoms; La is selected from -(CH 2 ) ma -O-(CH 2 ) 1a -, -(CH 2 ) ma -C(O)-(CH 2 ) 1a -isogroup, where the variables ma and 1a are independently selected from 0 to 4 integers; Ma is And a group selected from the group consisting of (i) to (iii); (i) a phenyl group which may be substituted with 1 to 3 substituents independently selected from the group consisting of Ra 1 , ORa 1 , a halogen atom, etc.; 1 to 3 optionally substituted naphthyl groups selected from the group consisting of Ra 1 , ORa 1 , halogen atoms, etc.; (iii) may be independently selected from 1 to 3 groups independently selected from the group consisting of Ra 1 , ORa 1 , and halogen atoms. a substituent substituted with 1 to 3 5 and 6 membered monocyclic heteroaryl groups independently selected from the group consisting of an oxygen atom, a nitrogen atom and a sulfur atom; wherein Ra 1 is independently selected from (a) To the group of (f), (a) a hydrogen atom, (b) a C 1 -C 6 alkyl group, (c) a phenyl group, and (d) have 1 to 4 members selected from the group consisting of an oxygen atom, a nitrogen atom, and a sulfur atom. 5 to 6 membered monocyclic heteroaryl or 8 to 10 membered bicyclic heteroaryl of the hetero atom of the group, (e) C 1 -C 3 alkyl-phenyl, and (f) having 1 to 4 An alkyl-heteroaryl group selected from the group consisting of an oxygen atom, a nitrogen atom and a sulfur atom; when Ra 1 is not a hydrogen atom, it may be independently selected from C 1 -C via 1 to 3 5 linear, branched or cyclic alkyl, C 1 -C 3 alkoxy, hydroxy, amine, C 1 -C 3 alkylamino, C 2 -C 6 dialkylamino, halogen atom, Substituted by a group of cyano and nitro groups. (Extracted from a part of the definition.)).

雖記載該專利文獻1之化合物可阻害KDR，而在VEGF誘發信號轉導途徑仲介之人類或其他哺乳類之疾病，尤其是視網膜症或早產兒視網膜症之處置方法中使用，惟，該專利中記載之化合物未記載或暗示具有Trk阻害活性，於該專利中，對於本發明化合物亦未具體記載。 Although the compound of Patent Document 1 is described as being capable of inhibiting KDR, it is used in a human or other mammalian disease in which VEGF induces a signal transduction pathway, particularly in a treatment method of retinopathy or retinopathy of prematurity, but it is described in the patent. The compound is not described or suggested to have a Trk inhibitory activity, and in this patent, the compound of the present invention is not specifically described.

又，專利文獻2雖記載通式(Ib)表示之化合物、該化合物之立體異構體、位置異構體及互變異構體係具有Ab1阻害活性、c-Met阻害活性、b-Raf阻害活性及c-Kit阻害活性，惟，對於具有Trk阻害活性無記載亦未暗示。又，該專利文獻2對於本發明化合物完全沒記載。 Further, in Patent Document 2, the compound represented by the formula (Ib), the stereoisomer, the positional isomer, and the tautomeric system of the compound have Ab1 inhibitory activity, c-Met inhibitory activity, b-Raf inhibitory activity, and c-Kit inhibits activity, but there is no record or inhibition of Trk inhibitory activity. Further, this Patent Document 2 does not describe the compound of the present invention at all.

(式中，Qb1及Qb2各自獨立，為選自由N及CH所成群組，Qb1及Qb2至少有1個為氮原子；各Db各自為選自由C、CH、C-Rb20、N-Zb3、氮原子、氧原子及硫原子所成群組，產生之環為選自由吡唑基、三唑基、異唑基、異噻唑基、唑基及噻二唑基所成群組；Eb為選自由苯基、吡啶基及嘧啶基所成群組；Xb2為選自由-O-、-S(CH2)nb-、-N(Rb3)(CH2)nb-、-(CH2)pb-所成群組；Qb1及Qb2只有一方為氮原子時，環Ab根據情況為選自可經取代基Zb2及Rb2等取代之環戊基、環己基、Gb1、Gb2、Gb3及Gb4所成群組；Gb1為選自吡咯基、呋喃基、噻吩基、唑基、噻唑基及吡唑基等群之雜芳基；Gb4為選自苯基、萘基、吡基、嗒基、三基、吡啶基及嘧啶基所成群組；Zb2為選自芳基、C1-C6烷基、C3-C8環烷基及支鏈狀C3-C7烷基等群；Rb2為選自取代芳基、取代Gb1、取代Gb4及鹵素原子等群；摘錄一部分基之定義。) (wherein Qb 1 and Qb 2 are each independently selected from the group consisting of N and CH, and at least one of Qb 1 and Qb 2 is a nitrogen atom; each Db is selected from C, CH, C-Rb 20 a group of N-Zb 3 , a nitrogen atom, an oxygen atom and a sulfur atom, the ring produced is selected from the group consisting of pyrazolyl, triazolyl and iso Azyl, isothiazolyl, The oxazolyl and thiadiazolyl groups are grouped; Eb is selected from the group consisting of phenyl, pyridyl and pyrimidinyl; and Xb 2 is selected from -O-, -S(CH 2 ) nb -, -N ( Rb 3 )(CH 2 ) nb -, -(CH 2 ) pb - groups; when only one of Qb 1 and Qb 2 is a nitrogen atom, the ring Ab is selected from the group of substituents Zb 2 and Rb 2 as the case may be. a group of isosubstituted cyclopentyl, cyclohexyl, Gb 1 , Gb 2 , Gb 3 and Gb 4 ; Gb 1 is selected from pyrrolyl, furyl, thienyl, a heteroaryl group such as azolyl, thiazolyl or pyrazolyl; Gb 4 is selected from the group consisting of phenyl, naphthyl and pyridyl Base Base, three a group of a pyridyl group and a pyrimidinyl group; Zb 2 is a group selected from the group consisting of an aryl group, a C1-C6 alkyl group, a C3-C8 cycloalkyl group, and a branched C3-C7 alkyl group; and Rb 2 is selected from the group consisting of a group such as an aryl group, a substituted Gb 1 , a substituted Gb 4 , and a halogen atom; the definition of a part of the base is extracted. )

另，專利文獻3雖記載通式(Ic)表示之化合物、該化合物之立體異構體、位置異構體及互變異構體係具有Ab1阻害活性、c-Met阻害活性及c-Kit阻害活性，惟對於具有Trk阻害活性無記載亦未暗示。又，該專利文獻3對於本發明化合物完全沒記 載。 Further, in Patent Document 3, the compound represented by the formula (Ic), the stereoisomer, the positional isomer, and the tautomeric system of the compound have Ab1 inhibitory activity, c-Met inhibitory activity, and c-Kit inhibitory activity. However, there is no record for the activity of Trk inhibition or suggestion. Further, this Patent Document 3 does not completely remember the compound of the present invention. Loaded.

(式中，各個Dc以獲得之環為吡唑之方式選自由C、CH、C-Rc20、N-Zc3及氮原子所成群組；Ec為選自由苯基、吡啶基及嘧啶基所成群組；Xc為選自-O-、-S(CH2)nc-、-N(Rc3)(CH2)nc-、-(CH2)Pc-所成群組；Ac根據情況，為選自由可經取代基Zc2及Rc2等取代之苯基、萘基、環戊基、環己基、Gc1、Gc2及Gc3所成群組之環系；Gc1為選自吡咯基、呋喃基、噻吩基、唑基、噻唑基及吡唑基等群之雜芳基；Gc2為選自吲哚基、吲哚啉基及異吲哚基等群之縮合二環式雜芳基；Gc3為選自氧雜環丁烷基、四氫呋喃基及吡咯啶基等群之雜環基；Zc2為選自芳基、C1-C6烷基、C3-C8環烷基及支鏈狀C3-C7烷基等群；Rc2為選自C1-C6烷基、支鏈狀C3-C8烷基及鹵素原子等群；摘錄一部分基之定義。) (wherein the ring obtained by each Dc is pyrazole in a manner selected from the group consisting of C, CH, C-Rc 20 , N-Zc 3 and a nitrogen atom; Ec is selected from the group consisting of phenyl, pyridyl and pyrimidinyl Groups; Xc is selected from the group consisting of -O-, -S(CH 2 ) nc -, -N(Rc 3 )(CH 2 ) nc -, -(CH 2 ) Pc -; Ac according to the situation And a ring system selected from the group consisting of a phenyl group, a naphthyl group, a cyclopentyl group, a cyclohexyl group, a Gc 1 group, a Gc 2 group, and a Gc 3 group which may be substituted with a substituent Zc 2 and Rc 2 or the like; Gc 1 is selected from the group consisting of Pyrrolyl, furyl, thienyl, a heteroaryl group of a group such as an azolyl group, a thiazolyl group or a pyrazolyl group; and Gc 2 is a condensed bicyclic heteroaryl group selected from the group consisting of a fluorenyl group, a porphyrin group and an isodecyl group; and Gc 3 is selected from the group consisting of a heterocyclic group such as an oxetane group, a tetrahydrofuranyl group or a pyrrolidinyl group; and Zc 2 is selected from the group consisting of an aryl group, a C1-C6 alkyl group, a C3-C8 cycloalkyl group, and a branched C3-C7 alkyl group. Group; Rc 2 is a group selected from the group consisting of a C1-C6 alkyl group, a branched C3-C8 alkyl group, and a halogen atom; the definition of a part of the base is extracted. )

[先行技術文獻] [Advanced technical literature] [專利文獻] [Patent Literature]

[專利文獻1]國際公開第2003/068228號手冊 [Patent Document 1] International Publication No. 2003/068228

[專利文獻2]國際公開第2008/131276號手冊 [Patent Document 2] International Publication No. 2008/131276

[專利文獻3]國際公開第2008/131227號手冊 [Patent Document 3] International Publication No. 2008/131227

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本發明之課題為創製對於Trk具有選擇性阻害活性之化合物，發現可作為以疼痛為代表之種種疾病之預防及/或治療藥使用之化合物。 The object of the present invention is to create a compound which has a selective inhibitory activity against Trk, and has been found to be a compound which can be used as a prophylactic and/or therapeutic agent for various diseases represented by pain.

本發明者人等為了發現對於Trk具有選擇性阻害活性並，可成為以疼痛為代表之種種疾病安全之預防及/或治療藥之化合物而進行深入研究之結果發現，後述通式(I)表示之化合物具有Trk阻害作用，具有優越之激酶選擇性，於體內試驗持續抑制NGF血管透過性亢進，因而完成本發明。 The inventors of the present invention have conducted intensive studies to find a compound which has a selective inhibitory activity against Trk and can be used as a preventive and/or therapeutic drug for various diseases represented by pain, and it has been found that the following general formula (I) shows The compound has a Trk inhibitory action, has superior kinase selectivity, and continuously inhibits NGF vascular hyperpermeability in an in vivo test, thus completing the present invention.

亦即，本發明係有關 That is, the invention is related

[1]通式(I)表示之化合物、其鹽、其N-氧化物、其溶劑化物或該等之前驅藥、 [1] a compound represented by the formula (I), a salt thereof, an N-oxide thereof, a solvate thereof, or the like,

(式中，環Cy1表示C3至10之單環式碳環或二環式碳環、或4至10員單環式雜環或二環式雜環、R1表示(1)鹵素原子、(2)可經鹵素原子或側氧基取代之C1至6烷基、(3)可經鹵素原子或C1至3烷基取代之C3至6環烷基、(4)可經鹵素原子或側氧基取代之C1至6烷基之碳原子以氧原子置換後之基、或(5)可經鹵素原子或C1至3烷基取代之C3至6環烷基之碳原子以氧原子置換後之基；R2表示(1)可經選自由(i)鹵素原子、(ii)羥基、(iii)-NH(C1至3烷基)、(iv)-N(C1至3烷基)2、(v)胺基、(vi)氰基、 (vii)硝基、(viii)C1至4烷基磺醯基、(ix)磺醯胺基、(x)C1至4烷基磺醯胺基、(xi)側氧基、(xii)羧基、(xiii)-C(O)(O-C1至4烷基)、(xiv)膦醯基氧基、(xv)-OP(O)(O-C1至4烷基)2、(xvi)胺基甲醯基、(xvii)C1至4烷基醯胺基及(xviii)C1至4烷基胺基甲酸酯基所成群組之取代基取代之C1至6烷基、C2至6烯基或C2至6炔基、(2)氫原子、(3)羥基、(4)羧基、(5)-C(O)(O-C1至4烷基)、(6)膦醯基氧基、(7)-OP(O)(O-C1至4烷基)2、(8)胺基、(9)氰基、(10)硝基、(11)C1至4烷基磺醯基、(12)磺醯胺基、 (13)C1至4烷基磺醯胺基、(14)側氧基、(15)胺基甲醯基、(16)C1至4烷基醯胺基、(17)C1至4烷基胺基甲酸酯基或 (wherein the ring Cy 1 represents a C 3 to 10 monocyclic carbocyclic ring or a bicyclic carbocyclic ring, or a 4 to 10 membered monocyclic heterocyclic ring or a bicyclic heterocyclic ring, and R 1 represents (1) a halogen atom, (2) a C1 to 6 alkyl group which may be substituted by a halogen atom or a pendant oxy group, (3) a C3 to 6 cycloalkyl group which may be substituted by a halogen atom or a C1 to 3 alkyl group, (4) may be passed through a halogen atom or a side a group in which an oxy-substituted C1 to 6-alkyl group is substituted with an oxygen atom, or (5) a carbon atom of a C3 to 6-cycloalkyl group which may be substituted by a halogen atom or a C1 to 3 alkyl group is replaced with an oxygen atom R 2 represents that (1) may be selected from (i) a halogen atom, (ii) a hydroxyl group, (iii) -NH (C1 to 3 alkyl), (iv)-N (C1 to 3 alkyl) 2 , (v) amine group, (vi) cyano group, (vii) nitro group, (viii) C1 to 4 alkyl sulfonyl group, (ix) sulfonamide group, (x) C1 to 4 alkyl sulfonamide a group, (xi) pendant oxy group, (xii) carboxy group, (xiii)-C(O) (O-C1 to 4 alkyl group), (xiv) phosphinyloxy group, (xv)-OP(O) ( O-C1 to 4-alkyl) 2 , (xvi) aminomethyl decyl, (xvii) C1 to 4 alkyl guanylamino and (xviii) C1 to 4 alkyl urethane groups Substituent substituted C1 to 6 alkyl, C2 to 6 alkenyl or C2 to 6 alkynyl, (2) hydrogen atom, (3) hydroxyl group , (4) carboxyl group, (5)-C(O) (O-C1 to 4 alkyl group), (6) phosphinyloxy group, (7)-OP(O) (O-C1 to 4 alkyl group) 2 , (8) amine group, (9) cyano group, (10) nitro group, (11) C1 to 4 alkyl sulfonyl group, (12) sulfonylamino group, (13) C1 to 4 alkyl sulfonium sulfonate Amino, (14) pendant oxy, (15) aminomethyl decyl, (16) C1 to 4 alkyl guanylamino, (17) C1 to 4 alkyl urethane or

箭頭a表示與環Cy1結合、X表示鍵結、氧原子、C=O或NH、環Cy2表示C3至10之單環式碳環或二環式碳環、或4至10員單環式雜環或二環式雜環；R6表示(1)可經選自由(i)鹵素原子、(ii)羥基、(iii)側氧基、(iv)-NH(C1至3烷基)、(v)-N(C1至3烷基)2、(vi)C1至6烷氧基、(vii)胺基、(viii)氰基、 (ix)硝基、(x)C1至4烷基磺醯基、(xi)磺醯胺基、(xii)C1至4烷基磺醯胺基、(xiii)羧基、(xiv)-C(O)(O-C1至4烷基)、(xv)膦醯基氧基、(xvi)-OP(O)(O-C1至4烷基)2、(xvii)胺基甲醯基、(xviii)C1至4烷基醯胺基及(xix)C1至4烷基胺基甲酸酯基所成群組之取代基取代之C1至6烷基、C2至6烯基、C2至6炔基或C3至6環烷基、(2)鹵素原子、(3)C1至4烷氧基、(4)膦醯基氧基、(5)-OP(O)(O-C1至4烷基)2、(6)磺醯胺基、(7)側氧基、(8)-NH(C1至3烷基)、(9)-N(C1至3烷基)2、(10)羧基、(11)-C(O)(O-C1至4烷基)、(12)胺基甲醯基、(13)C1至4烷基醯胺基、 (14)羥基、(15)胺基、(16)氰基、(17)硝基、(18)C1至4烷基磺醯基、(19)C1至4烷基磺醯胺基或(20)C1至4烷基胺基甲酸酯基、A1及A2各自獨立，表示=CR3-、=CH-或=N-、A3、A4、A5及A6各自獨立地表示=CR4-或=N-；R3表示(1)鹵素原子或(2)可經鹵素原子取代之C1至3烷基或C1至3烷氧基；R4表示(1)鹵素原子、(2)可經鹵素原子取代之C1至3烷基或C1至3烷氧基或(3)氫原子；Y表示氧原子、可經氧化之硫原子、亞甲基或C=O；Z表示形成 或 之環之碳原子以氧原子置換後之基；R5表示鹵素原子、羥基或可經羥基取代之C1至4烷基；R7各自獨立地為(1)可經選自由(i)鹵素原子、(ii)C3至6環烷基、(iii)羥基、(iv)側氧基及(v)4至6員單環式雜環所成群組之取代基取代之C1至6烷基、C3至6環烷基、C1至6烷基之碳原子以氧原子置換後之基、C3至6環烷基之碳原子以氧原子置換後之基或(2)氫原子；箭頭b、c、d及e表示與噻唑環結合、p表示0至5之整數、q表示0至7之整數、r表示0至2之整數、w表示1至5之整數、u表示0至2之整數。惟，p、q、r及u各別表示2以上之整數時，R1、R3、R5及R6各自獨立，可相同亦可不同。) The arrow a represents a bond with the ring Cy 1 , X represents a bond, an oxygen atom, C=O or NH, the ring Cy 2 represents a C 3 to 10 monocyclic carbocyclic ring or a bicyclic carbocyclic ring, or a 4 to 10 membered single ring. a heterocyclic or bicyclic heterocyclic ring; R 6 represents that (1) may be selected from (i) a halogen atom, (ii) a hydroxyl group, (iii) a pendant oxy group, (iv) -NH (C1 to 3 alkyl group). , (v)-N (C1 to 3 alkyl) 2 , (vi) C1 to 6 alkoxy, (vii) amine, (viii) cyano, (ix) nitro, (x) C1 to 4 alkane Sulfosyl, (xi) sulfonylamino, (xii) C1 to 4 alkylsulfonylamino, (xiii) carboxyl, (xiv)-C(O)(O-C1 to 4 alkyl), Xv) phosphinyloxy, (xvi)-OP(O)(O-C1 to 4 alkyl) 2 , (xvii) aminomethyl decyl, (xviii) C1 to 4 alkyl guanylamino and (xix a C1 to 6 alkyl group, a C2 to 6 alkenyl group, a C2 to 6 alkynyl group or a C3 to 6 cycloalkyl group, (2) a halogen substituted with a group of a C1 to 4 alkyl carbamate group Atom, (3) C1 to 4 alkoxy, (4) phosphinyloxy, (5)-OP (O) (O-C1 to 4 alkyl) 2 , (6) sulfonylamino, (7) a sideoxy group, (8)-NH (C1 to 3 alkyl), (9)-N (C1 to 3 alkyl) 2 , (10) carboxyl, (11)-C(O) (O-C1 to 4 alkyl), (12) aminomethyl decyl, (13) C1 to 4 alkyl guanylamino, (14) Base, (15) amine group, (16) cyano group, (17) nitro group, (18) C1 to 4 alkyl sulfonyl group, (19) C1 to 4 alkyl sulfonylamino group or (20) C1 to The 4 alkyl urethane groups, A 1 and A 2 are each independently, and represent =CR 3 -, =CH- or =N-, A 3 , A 4 , A 5 and A 6 each independently represent =CR 4 - or = N-; R 3 represents (1) a halogen atom or (2) a C1 to 3 alkyl group or a C1 to 3 alkoxy group which may be substituted by a halogen atom; R 4 represents (1) a halogen atom, (2) a C1 to 3 alkyl group or a C1 to 3 alkoxy group or a (3) hydrogen atom substituted by a halogen atom; Y represents an oxygen atom, an oxidizable sulfur atom, a methylene group or a C=O; Z represents formation or a ring in which a carbon atom is replaced by an oxygen atom; R 5 represents a halogen atom, a hydroxyl group or a C1 to 4 alkyl group which may be substituted by a hydroxyl group; and R 7 is independently independently (1) may be selected from (i) a halogen atom And (ii) a C1 to 6 alkyl group substituted with a substituent of a C3 to 6 cycloalkyl group, (iii) a hydroxyl group, (iv) a pendant oxy group, and (v) a 4 to 6 membered monocyclic heterocyclic ring, a group in which a carbon atom of a C3 to 6 cycloalkyl group, a C1 to 6 alkyl group is replaced by an oxygen atom, a carbon atom of a C3 to 6 cycloalkyl group is substituted with an oxygen atom, or (2) a hydrogen atom; an arrow b, c And d and e represent a combination with a thiazole ring, p represents an integer of 0 to 5, q represents an integer of 0 to 7, r represents an integer of 0 to 2, w represents an integer of 1 to 5, and u represents an integer of 0 to 2. However, when p, q, r, and u each represent an integer of 2 or more, R 1 , R 3 , R 5 , and R 6 are each independently and may be the same or different. )

[2].如上述[1]記載之化合物，其中，通式(I)為 [2] The compound according to the above [1], wherein the formula (I) is

(式中，所有符號與上述[1]記載之符號同意義。) (In the formula, all symbols have the same meaning as the symbols described in [1] above.)

[3].如上述[2]記載之化合物，其中，通式(I-1)為 [3] The compound according to the above [2], wherein the formula (I-1) is

(式中，所有符號與上述[1]記載之符號同意義。) (In the formula, all symbols have the same meaning as the symbols described in [1] above.)

[4].如上述[2]或上述[3]記載之化合物，其中，環Cy1為苯環或5至6員之單環式芳族雜環。 [4] As described above the compound according to [2] or [3], wherein Cy 1 is a single ring or a benzene ring of 5-6 ring aromatic heterocyclic ring.

[5].如上述[1]至[4]中任何一項記載之化合物，其中，A1及A2任何一方為=N-且另一方為=CH-，或雙方均為=N-，A3、A4、A5及A6為=CH-。 [5] The compound according to any one of the above [1] to [4] wherein either one of A 1 and A 2 is =N- and the other is =CH-, or both are =N-, A 3 , A 4 , A 5 and A 6 are =CH-.

[6].如上述[1]記載之化合物，其中，通式(I)為 或 [6] The compound according to the above [1], wherein the formula (I) is or

(式中，pa表示0至4之整數，pb表示0至3之整數，其他之符號表示與上述[1]記載者同意義。惟，pa及pb各別表示2以上之整數時，R1可為相同或不同。) (wherein, pa represents an integer of 0 to 4, and pb represents an integer of 0 to 3. The other symbols represent the same meaning as those described in the above [1]. However, when pa and pb each represent an integer of 2 or more, R 1 Can be the same or different.)

[7].如上述[6]記載之化合物，其中，A1及A2任何一方為=N-且另一方為=CH-，或雙方均為=N-，A3、A4、A5及A6為=CH-。 [7] The compound according to the above [6], wherein either one of A 1 and A 2 is =N- and the other is =CH-, or both are =N-, A 3 , A 4 , A 5 And A 6 is =CH-.

[8].如上述[1]記載之化合物，其中，通式(I)為 [8] The compound according to the above [1], wherein the formula (I) is

(式中，所有符號與上述[1]及[6]記載之符號同意義。) (In the formula, all symbols have the same meaning as the symbols described in [1] and [6] above.)

[9].如上述[8]記載之化合物，其中，A1及A2任何一方為=N-且另一方為=CH-，或雙方均為=N-，A3、A4、A5及A6為=CH-。 [9] The compound according to the above [8], wherein either one of A 1 and A 2 is =N- and the other is =CH-, or both are =N-, A 3 , A 4 , A 5 And A 6 is =CH-.

[10].一種醫藥組成物，係含有上述[1]記載之通式(I)表示之化合物、其鹽、其N-氧化物、其溶劑化物或該等之前驅藥作為有效成分。 [10] A pharmaceutical composition comprising the compound represented by the above formula (I), a salt thereof, an N-oxide thereof, a solvate thereof, or the prodrug as an active ingredient.

[11].如上述[10]記載之醫藥組成物，其為Trk阻害劑。 [11] The pharmaceutical composition according to [10] above which is a Trk inhibitor.

[12].如上述[10]記載之醫藥組成物，其為疼痛、搔癢症、下部尿路障害、氣喘、過敏性鼻炎、發炎性腸疾病或查加斯病之預防及/或治療劑。 [12] The pharmaceutical composition according to the above [10], which is a preventive and/or therapeutic agent for pain, pruritus, lower urinary tract dysfunction, asthma, allergic rhinitis, inflammatory bowel disease or Chagas disease.

[13].如上述[12]記載之醫藥組成物，其中，疼痛為變形性關節炎伴隨之疼痛、癌性疼痛、慢性腰痛症、骨質疏鬆症伴隨之腰痛、骨折痛、風濕性關節炎伴隨之疼痛、神經障害性疼痛、帶狀疱疹後疼痛、糖尿病性神經障害伴隨之疼痛、纖維肌痛症、胰臟炎伴隨之疼痛、間質性膀胱炎伴隨之疼痛、子宮內膜症伴隨之疼痛、過敏性腸症候群伴隨之疼痛、偏頭痛或齒髓炎伴隨之疼痛。 [13] The pharmaceutical composition according to the above [12], wherein the pain is accompanied by pain associated with osteoarthritis, cancer pain, chronic low back pain, low back pain associated with osteoporosis, fracture pain, and rheumatoid arthritis Pain, neurological pain, post-herpetic pain, pain associated with diabetic neurological disorders, fibromyalgia, pain associated with pancreatitis, pain associated with interstitial cystitis, pain associated with endometriosis , pain associated with irritable bowel syndrome, pain associated with migraine or pulpitis.

[14].一種醫藥，為由上述[1]記載之通式(I)表示之化合物、其鹽、其N-氧化物、其溶劑化物或該等之前驅藥，與選自對乙醯胺基酚(acetaminophen)，非類固醇性抗炎症藥、鴉片類藥、抗憂鬱藥、抗癲癇藥、N-甲基-D-天冬胺酸拮抗藥、肌肉鬆弛藥、抗心律不整藥、類固醇藥及雙磷酸鹽藥之至少一種以上組合而形成。 [14] A pharmaceutical composition comprising the compound represented by the above formula (1), a salt thereof, an N-oxide thereof, a solvate thereof, or the prodrug, and a phenacetamide selected from the group consisting of p-acetamide Acetaminophen, non-steroidal anti-inflammatory drugs, opioids, antidepressants, antiepileptics, N-methyl-D-aspartate antagonists, muscle relaxants, antiarrhythmics, steroids And at least one or more combinations of bisphosphonates are formed.

[15].一種疼痛、搔癢症、下部尿路障害、氣喘、過敏性鼻炎、發炎性腸疾病或查加斯病之預防及/或治療方法，其特徵為於病患投予有效量之上述[1]記載之通式(I)表示之化合物、其鹽、其N-氧化物、其溶劑化物或該等之前驅藥、 [15] A method for preventing and/or treating pain, pruritus, lower urinary tract dysfunction, asthma, allergic rhinitis, inflammatory bowel disease or Chagas disease, characterized in that the patient is administered an effective amount of the above [1] The compound represented by the formula (I), a salt thereof, an N-oxide thereof, a solvate thereof, or the like,

[16].如上述[1]記載之通式(I)表示之化合物、其鹽、其N-氧化物、其溶劑化物或該等之前驅藥，係用於疼痛、搔癢症、下部尿路障 害、氣喘、過敏性鼻炎、發炎性腸疾病或查加斯病之預防及/或治療、 [16] The compound represented by the formula (I), the salt thereof, the N-oxide thereof, the solvate thereof or the prodrug of the above-mentioned [1], which is used for pain, pruritus, lower urinary tract Prevention and/or treatment of harm, asthma, allergic rhinitis, inflammatory bowel disease or Chagas disease,

[17].一種Trk阻害方法，其特徵為於病患投予有效量之上述[1]記載之通式(I)表示之化合物、其鹽、其N-氧化物、其溶劑化物或該等之前驅藥、 [17] A method for inhibiting Trk, which comprises administering to a patient an effective amount of a compound represented by the above formula (I), a salt thereof, an N-oxide thereof, a solvate thereof or the like Before the drug,

[18].一種上述[1]記載之通式(I)表示之化合物、其鹽、其N-氧化物、其溶劑化物或該等之前驅藥之使用，用於製造疼痛、搔癢症、下部尿路障害、氣喘、過敏性鼻炎、發炎性腸疾病或查加斯病之預防及/或治療劑。 [18] A compound represented by the above formula (1), a salt thereof, an N-oxide thereof, a solvate thereof, or the use of the prodrug, for producing pain, pruritus, lower part A preventive and/or therapeutic agent for urinary tract disorders, asthma, allergic rhinitis, inflammatory bowel disease or Chagas disease.

本發明化合物具有Trk阻害活性。另，本發明化合物具有優越之激酶選擇性。又，由於本發明化合物持續抑制於體內試驗之NGF血管透過性亢進，對於Trk參予之疾病，例如疼痛、搔癢症、下部尿路障害、氣喘、過敏性鼻炎、發炎性腸疾病或查加斯病等疾病為安全之預防及/或治療藥。 The compounds of the invention have Trk inhibitory activity. In addition, the compounds of the invention have superior kinase selectivity. Further, since the compound of the present invention continues to inhibit NGF vascular hyperpermeability in an in vivo test, diseases involving Trk such as pain, pruritus, lower urinary tract dysfunction, asthma, allergic rhinitis, inflammatory bowel disease or Chagas Diseases such as diseases are safe preventive and/or therapeutic drugs.

以下，將本發明作詳細說明。 Hereinafter, the present invention will be described in detail.

本發明中，環Cy1表示之「C3至10之單環式碳環或二環式碳環」，為例如環丙烷、環丁烷、環戊烷、環己烷、環庚烷、環辛烷、環壬烷、環癸烷、環戊烯、環己烯、環庚烯、環辛烯、環戊二烯、環己二烯、環庚二烯、環辛二烯、苯、戊搭烯、全氫戊搭烯、薁、全氫薁、茚、全氫茚、茚烷、萘、二氫萘、四氫萘 及全氫萘環等。 In the present invention, the ring Cy 1 represents "C3 to 10 monocyclic carbocyclic ring or bicyclic carbocyclic ring", and is, for example, cyclopropane, cyclobutane, cyclopentane, cyclohexane, cycloheptane, cyclooctane. Alkane, cyclodecane, cyclodecane, cyclopentene, cyclohexene, cycloheptene, cyclooctene, cyclopentadiene, cyclohexadiene, cycloheptadiene, cyclooctadiene, benzene, pentane Alkene, perhydropentene, anthracene, perhydroanthracene, anthracene, perhydrohydroquinone, decane, naphthalene, dihydronaphthalene, tetrahydronaphthalene, and perhydronaphthalene ring.

本發明中，環Cy1表示之「4至10員單環式雜環或二環式雜環」為例如氧雜環丁烷、氮雜環丁烷、吡咯、咪唑、三唑、四唑、吡唑、吡啶、哌啶、哌、吡、嘧啶、嗒、吖呯、二吖呯、呋喃、吡喃、呯、噻吩、噻喃、噻呯、唑、異唑、噻唑、異噻唑、呋吖、二唑、、二、吖呯、二吖呯、噻二唑、噻、噻二、噻吖呯、噻二吖呯、吲哚、異吲哚、吲哚、苯并呋喃、異苯并呋喃、苯并噻吩、異苯并噻吩、吲唑、喹啉、異喹啉、喹、嘌呤、酞、喋啶、萘啶、喹喔啉、喹唑啉、噌啉、苯并唑、苯并噻唑、苯并咪唑、苯并二茂、苯并硫醇、色烯、苯并呋吖、苯并噻二唑、苯并三唑、吡咯啉、吡咯啶、咪唑啉、咪唑啶、三唑啉、三唑啶、四唑啉、四唑啶、吡唑啉、吡唑啶、二氫吡啶、四氫吡啶、哌啶、二氫吡、四氫吡、哌、二氫嘧啶、四氫嘧啶、全氫嘧啶、二氫嗒、四氫嗒、全氫嗒、二氫吖呯、四氫吖呯、全氫吖呯、二氫二吖呯、四氫二吖呯、全氫二吖呯、二氫呋喃、四氫呋喃、二氫吡喃、四氫吡喃、二氫呯、四氫呯、全氫呯、二氫噻吩、四氫噻吩、二氫噻喃、四氫噻喃、二氫噻呯、四氫噻呯、全氫噻呯、二氫唑、四氫唑(唑啶)、二氫異唑、四氫異唑(異唑啶)、二氫噻唑、四氫噻唑(噻唑啶)、二氫異噻唑、四氫異噻唑(異噻唑啶)、二氫呋吖、四氫呋吖、二氫二唑、四氫二唑(二唑啶)、二氫、四氫、二氫二、四氫二、二氫吖呯、四氫吖呯、全氫吖呯、二氫二吖呯、四氫二吖呯、全氫二吖呯、二氫噻二唑、四氫噻二唑(噻二唑啶)、二氫噻、四氫 噻、二氫噻二、四氫噻二、二氫噻吖呯、四氫噻吖呯、全氫噻吖呯、二氫噻二吖呯、四氫噻二吖呯、全氫噻二吖呯、嗎啉、硫代嗎啉、噻仙(oxathiane)、吲哚啉、異吲哚啉、二氫苯并呋喃、全氫苯并呋喃、二氫異苯并呋喃、全氫異苯并呋喃、二氫苯并噻吩、全氫苯并噻吩、二氫異苯并噻吩、全氫異苯并噻吩、二氫吲唑、全氫吲唑、二氫喹啉、四氫喹啉、全氫喹啉、二氫異喹啉、四氫異喹啉、全氫異喹啉、二氫酞、四氫酞、全氫酞、二氫萘啶、四氫萘啶、全氫萘啶、二氫喹喔啉、四氫喹喔啉、全氫喹喔啉、二氫喹唑啉、四氫喹唑啉、全氫喹唑啉、二氫噌啉、四氫噌啉、全氫噌啉、苯并噻仙、二氫苯并、二氫苯并噻、吡嗎啉、二氫苯并唑、全氫苯并唑、二氫苯并噻唑、全氫苯并噻唑、二氫苯并咪唑、全氫苯并咪唑、二戊烷、二烷、二茚烷、苯并二烷、硫代色滿(thiochroman)、二氫苯并二英、二氫苯并氧硫雜環己二烯及色滿環等。 In the present invention, the "C4 to 10 member monocyclic heterocyclic ring or bicyclic heterocyclic ring" represented by the ring Cy 1 is, for example, oxetane, azetidine, pyrrole, imidazole, triazole, tetrazole, Pyrazole, pyridine, piperidine, piperazine Pyr Pyrimidine , hydrazine, diterpenes, furan, pyran, Ruthenium, thiophene, thiopyran, thiazide, Azole Oxazole, thiazole, isothiazole, furazan, Diazole, , two , Oh, Diterpenoid, thiadiazole, thiophene Thia , thiazide, thiazepine, hydrazine, isoindole, hydrazine , benzofuran, isobenzofuran, benzothiophene, isobenzothiophene, carbazole, quinoline, isoquinoline, quin , 嘌呤, 酞 , acridine, naphthyridine, quinoxaline, quinazoline, porphyrin, benzo Oxazole, benzothiazole, benzimidazole, benzodiazepine Mao, benzo Mercaptan, chromene, benzofurazan, benzothiadiazole, benzotriazole, pyrroline, pyrrolidine, imidazoline, imidazolium, triazoline, triazole, tetrazoline, tetrazolidine, Pyrazoline, pyrazolidine, dihydropyridine, tetrahydropyridine, piperidine, dihydropyridyl Tetrahydropyridyl Piper , dihydropyrimidine, tetrahydropyrimidine, perhydropyrimidine, indoline Tetrahydroanthraquinone All hydroquinone , indoline, tetrahydroanthracene, perhydroanthraquinone, dihydroindrene, tetrahydrofuran, perhydrodifluorene, dihydrofuran, tetrahydrofuran, dihydropyran, tetrahydropyran, Dihydrogen Helium, tetrahydrogen Helium, all hydrogen Anthracene, dihydrothiophene, tetrahydrothiophene, dihydrothiopyran, tetrahydrothiopyran, dihydrothiazide, tetrahydrothiazolidine, perhydrothiazolidine, dihydrogen Oxazole, tetrahydrogen Azole Oxazolidine) Azole, tetrahydroiso Azole Zolidine, dihydrothiazole, tetrahydrothiazole (thiazolidine), dihydroisothiazole, tetrahydroisothiazole (isothiazolidine), dihydrofurazan, tetrahydrofurazan, dihydrogen Diazole, tetrahydrogen Diazole Diazolidine), dihydrogen Tetrahydrogen Dihydrogen two Tetrahydrogen two Dihydrogen Helium, tetrahydrogen Helium, all hydrogen Helium, dihydrogen Diterpene, tetrahydrogen Diterpene, all hydrogen Diterpene, dihydrothiadiazole, tetrahydrothiadiazole (thiadiazolidine), dihydrothiazide Tetrahydrothiazide Dihydrothiazide Tetrahydrothiazide , dihydrothiazide, tetrahydrothiazide, perhydrothiazolidine, dihydrothiadiazine, tetrahydrothiadiazine, perhydrothiadiazine, morpholine, thiomorpholine, Oxalthiane, porphyrin, isoporphyrin, dihydrobenzofuran, perhydrobenzofuran, dihydroisobenzofuran, perhydroisobenzofuran, dihydrobenzothiophene, perhydrobenzene And thiophene, dihydroisobenzothiophene, perhydroisobenzothiophene, dihydrocarbazole, perhydrocarbazole, dihydroquinoline, tetrahydroquinoline, perhydroquinoline, dihydroisoquinoline, tetrahydrogen Isoquinoline, perhydroisoquinoline, indoline Tetrahydroanthraquinone All hydroquinone , dihydronaphthyridine, tetrahydronaphthyridine, perhydronaphthyridine, dihydroquinoxaline, tetrahydroquinoxaline, perhydroquinoxaline, dihydroquinazoline, tetrahydroquinazoline, perhydroquinazoline Porphyrin, dihydroporphyrin, tetrahydroporphyrin, perhydroporphyrin, benzo Thioxan, dihydrobenzo Dihydrobenzothiazide Pyr Morpholine, dihydrobenzo Oxazole, all hydrogen benzo Azole, dihydrobenzothiazole, perhydrobenzothiazole, dihydrobenzimidazole, perhydrobenzimidazole, two Pentane, two Alkane, two Decane, benzoic acid Alkane, thiochroman, dihydrobenzoic acid English, dihydrobenzoxylene thicyclodiene and color ring.

本發明中，R1表示之「可經鹵素原子或側氧基取代之C1至6烷基」中之「C1至6烷基」為甲基、乙基、正丙基、異丙基、正丁基、第二丁基、第三丁基、異丁基、戊基、1-甲基丁基、2-甲基丁基、3-甲基丁基、1，1-二甲基丙基、1，2-二甲基丙基、2，2-二甲基丙基、己基、1-甲基戊基、2-甲基戊基、3-甲基戊基、4-甲基戊基、1，1-二甲基丁基、1，2-二甲基丁基、1，3-二甲基丁基、2，2-二甲基丁基、2，3-二甲基丁基、1-甲基-1-乙基丙基、2-甲基-2-乙基丙基、1-乙基丁基、2-乙基丁基及1，1-二甲基戊基等。 In the present invention, the "C1 to 6 alkyl group" in the "C1 to 6 alkyl group which may be substituted by a halogen atom or a pendant oxy group" represented by R 1 is a methyl group, an ethyl group, a n-propyl group, an isopropyl group, or a positive group. Butyl, t-butyl, tert-butyl, isobutyl, pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 1,1-dimethylpropyl 1,2-dimethylpropyl, 2,2-dimethylpropyl, hexyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl , 1-methyl-1-ethylpropyl, 2-methyl-2-ethylpropyl, 1-ethylbutyl, 2-ethylbutyl and 1,1-dimethylpentyl, and the like.

本發明中，R1表示之「可經鹵素原子或C1至3烷基 取代之C3至6環烷基」中之「C3至6環烷基」為環丙基、環丁基、環戊基及環己基。 In the present invention, R 1 represents the "may be a halogen atom or a C1 to 3 alkyl substituted cycloalkyl group of C3 to 6" in the "C3 to 6 cycloalkyl" is cyclopropyl, cyclobutyl, cyclopentyl And cyclohexyl.

本發明中，R1表示之「可經鹵素原子或C1至3烷基取代之C3至6環烷基」中之「C1至3烷基」為甲基、乙基、正丙基及異丙基。 In the present invention, R 1 represents the "may be substituted with a halogen atom or of a C3 to C6 cycloalkyl C1 to C3 alkyl" in the "C1 to 3 alkyl" is methyl, ethyl, n-propyl and isopropyl base.

本發明中，R1表示之「可經鹵素原子或側氧基取代之C1至6烷基之碳原子以氧原子取代之基」中之「C1至6烷基之碳原子以氧原子取代之基」為該C1至6烷基之1個亞甲基(-CH2-)以氧原子(-O-)取代之基，例如為羥基、甲氧基、羥基甲基、乙氧基、甲氧基甲基、2-羥基乙基、1-羥基乙基、2-羥基丙基、異丙氧基、1-甲基-2-羥基乙基、1-甲氧基乙基、1-羥基丙基、1-羥基-1-甲基乙基、1-羥基-1-甲基丙基、2-羥基-1-甲基丙基及2-羥基2-甲基丙基等。 In the present invention, R 1 represents a "C1 to 6 alkyl group in which a carbon atom of a C1 to 6 alkyl group which may be substituted by a halogen atom or a pendant oxy group is substituted with an oxygen atom" is substituted with an oxygen atom. The group is a group in which one methylene group (-CH 2 -) of the C1 to 6 alkyl group is substituted with an oxygen atom (-O-), and is, for example, a hydroxyl group, a methoxy group, a hydroxymethyl group, an ethoxy group, or a group Oxymethyl, 2-hydroxyethyl, 1-hydroxyethyl, 2-hydroxypropyl, isopropoxy, 1-methyl-2-hydroxyethyl, 1-methoxyethyl, 1-hydroxy Propyl, 1-hydroxy-1-methylethyl, 1-hydroxy-1-methylpropyl, 2-hydroxy-1-methylpropyl and 2-hydroxy 2-methylpropyl, and the like.

本發明中，R1表示之「可經鹵素原子或C1至3烷基取代之C3至6環烷基之碳原子以氧原子取代之基」表示可經鹵素原子、C1至3烷基、或C1至3烷基之碳原子以氧原子取代之基取代之C3至6環烷基之碳原子以氧原子取代之基。 In the present invention, R 1 represents "a group in which a carbon atom of a C3 to 6 cycloalkyl group which may be substituted by a halogen atom or a C1 to 3 alkyl group is substituted with an oxygen atom" means a halogen atom, a C1 to 3 alkyl group, or The carbon atom of the C1 to 3 alkyl group is substituted with a group substituted with an oxygen atom, and the carbon atom of the C3 to 6 cycloalkyl group is substituted with an oxygen atom.

此處，「C3至6環烷基之碳原子以氧原子取代之基」為該C3至6環烷基之1個亞甲基(-CH2-)以氧原子(-O-)取代之基，為例如環氧乙烷基、1-氧雜環丁烷基、2-氧雜環丁烷基、1-四氫呋喃基、2-四氫呋喃基、1-四氫-2H-吡喃基、2-四氫-2H-吡喃基及3-四氫-2H-吡喃基等。 Here, "the carbon atom of the C3 to 6 cycloalkyl group is substituted with an oxygen atom" is a methylene group (-CH 2 -) of the C3 to 6 cycloalkyl group substituted with an oxygen atom (-O-). The group is, for example, an oxiranyl group, a 1-oxetanyl group, a 2-oxetanyl group, a 1-tetrahydrofuranyl group, a 2-tetrahydrofuranyl group, a 1-tetrahydro-2H-pyranyl group, 2 - tetrahydro-2H-pyranyl and 3-tetrahydro-2H-pyranyl and the like.

又，「C1至3烷基」為甲基、乙基、正丙基及異丙基。 Further, the "C1 to 3 alkyl group" is a methyl group, an ethyl group, a n-propyl group or an isopropyl group.

「C1至3烷基之碳原子以氧原子取代之基」為該C1至3烷基之1個亞甲基(-CH2-)以氧原子(-O-)取代之基，為例如羥基、甲氧基、羥基甲基、乙氧基、甲氧基甲基、2-羥基乙基及1-羥基乙基等。 The "C1 to 3 alkyl group having a carbon atom substituted with an oxygen atom" is a group in which one methylene group (-CH 2 -) of the C1 to 3 alkyl group is substituted with an oxygen atom (-O-), and is, for example, a hydroxyl group. , methoxy, hydroxymethyl, ethoxy, methoxymethyl, 2-hydroxyethyl and 1-hydroxyethyl.

本發明中，R2表示之「可經選自由(i)鹵素原子、(ii)羥基、(iii)-NH(C1至3烷基)、(iv)-N(C1至3烷基)2、(v)胺基、(vi)氰基、(vii)硝基、(viii)C1至4烷基磺醯基、(ix)磺醯胺基、(x)C1至4烷基磺醯胺基、(xi)側氧基、(xii)羧基、(xiii)-C(O)(O-C1至4烷基)、(xiv)膦醯基氧基、(xv)-OP(O)(O-C1至4烷基)2、(xvi)胺基甲醯基、(xvii)C1至4烷基醯胺基及(xviii)C1至4烷基胺基甲酸酯基所成群組之取代基取代之C1至6烷基」中之「C1至6烷基」為甲基、乙基、正丙基、異丙基、正丁基、第二丁基、第三丁基、異丁基、戊基、1-甲基丁基、2-甲基丁基、3-甲基丁基、1，1-二甲基丙基、1，2-二甲基丙基、2，2-二甲基丙基、己基、1-甲基戊基、2-甲基戊基、3-甲基戊基、4-甲基戊基、1，1-二甲基丁基、1，2-二甲基丁基、1，3-二甲基丁基、2，2-二甲基丁基、2，3-二甲基丁基、1-甲基-1-乙基丙基、2-甲基-2-乙基丙基、1-乙基丁基、2-乙基丁基及1，1-二甲基戊基等。 In the present invention, R 2 represents "may be selected from (i) a halogen atom, (ii) a hydroxyl group, (iii) - NH (C1 to 3 alkyl group), (iv)-N (C1 to 3 alkyl group) 2 , (v) amine group, (vi) cyano group, (vii) nitro group, (viii) C1 to 4 alkyl sulfonyl group, (ix) sulfonamide group, (x) C1 to 4 alkyl sulfonamide a group, (xi) pendant oxy group, (xii) carboxy group, (xiii)-C(O) (O-C1 to 4 alkyl group), (xiv) phosphinyloxy group, (xv)-OP(O) ( O-C1 to 4-alkyl) 2 , (xvi) aminomethyl decyl, (xvii) C1 to 4 alkyl guanylamino and (xviii) C1 to 4 alkyl urethane groups "C1 to 6 alkyl" in the substituent substituted C1 to 6 alkyl" is methyl, ethyl, n-propyl, isopropyl, n-butyl, t-butyl, t-butyl, isobutyl Base, pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 2,2- Dimethylpropyl, hexyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1,1-dimethylbutyl, 1,2- Dimethyl butyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 1-methyl-1-ethylpropyl, 2- Methyl-2-ethylpropyl 1-ethylbutyl, 2-ethylbutyl and 1,1-dimethyl-pentyl and the like.

本發明中，R2表示之「可經選自由(i)鹵素原子、(ii)羥基、(iii)-NH(C1至3烷基)、(iv)-N(C1至3烷基)2、(v)胺基、(vi)氰基、(vii)硝基、(viii)C1至4烷基磺醯基、(ix)磺醯胺基、(x)C1至4烷基磺醯胺基、(xi)側氧基、(xii)羧基、(xiii)-C(O)(O-C1至4烷基)、(xiv)膦醯基氧基、(xv)-OP(O)(O-C1至4烷基)2、(xvi)胺基甲醯基、(xvii)C1至4烷基醯胺基及(xviii)C1至4烷基胺基甲酸酯 基所成群組之取代基取代之C2至6烯基」中之「C2至6烯基」為乙烯基、1-丙烯基、2-丙烯基、1-丁烯基、2-丁烯基、3-丁烯基、1-戊烯基、2-戊烯基、3-戊烯基、4-戊烯基、3-甲基-1-丁烯基、3-甲基-2-丁烯基、3-甲基-3-丁烯基、1-己烯基、2-己烯基、3-己烯基、4-己烯基及5-己烯基等。 In the present invention, R 2 represents "may be selected from (i) a halogen atom, (ii) a hydroxyl group, (iii) - NH (C1 to 3 alkyl group), (iv)-N (C1 to 3 alkyl group) 2 , (v) amine group, (vi) cyano group, (vii) nitro group, (viii) C1 to 4 alkyl sulfonyl group, (ix) sulfonamide group, (x) C1 to 4 alkyl sulfonamide a group, (xi) pendant oxy group, (xii) carboxy group, (xiii)-C(O) (O-C1 to 4 alkyl group), (xiv) phosphinyloxy group, (xv)-OP(O) ( O-C1 to 4-alkyl) 2 , (xvi) aminomethyl decyl, (xvii) C1 to 4 alkyl guanylamino and (xviii) C1 to 4 alkyl urethane groups The "C2 to 6 alkenyl group" in the substituent substituted C2 to 6 alkenyl group is a vinyl group, a 1-propenyl group, a 2-propenyl group, a 1-butenyl group, a 2-butenyl group, a 3-butenyl group. , 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 3-methyl-1-butenyl, 3-methyl-2-butenyl, 3-methyl Alkyl-3-butenyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl and the like.

本發明中，R2表示之「可經選自由(i)鹵素原子、(ii)羥基、(iii)-NH(C1至3烷基)、(iv)-N(C1至3烷基)2、(v)胺基、(vi)氰基、(vii)硝基、(viii)C1至4烷基磺醯基、(ix)磺醯胺基、(x)C1至4烷基磺醯胺基、(xi)側氧基、(xii)羧基、(xiii)-C(O)(O-C1至4烷基)、(xiv)膦醯基氧基、(xv)-OP(O)(O-C1至4烷基)2、(xvi)胺基甲醯基、(xvii)C1至4烷基醯胺基及(xviii)C1至4烷基胺基甲酸酯基所成群組之取代基取代之C2至6炔基」中之「C2至6炔基」為乙炔基、1-丙炔基、2-丙炔基、1-丁炔基、2-丁炔基、3-丁炔基、1-戊炔基、2-戊炔基、3-戊炔基、4-戊炔基、3-甲基-1-丁炔基、1-己炔基、2-己炔基、3-己炔基、4-己炔基及5-己炔基等。 In the present invention, R 2 represents "may be selected from (i) a halogen atom, (ii) a hydroxyl group, (iii) - NH (C1 to 3 alkyl group), (iv)-N (C1 to 3 alkyl group) 2 , (v) amine group, (vi) cyano group, (vii) nitro group, (viii) C1 to 4 alkyl sulfonyl group, (ix) sulfonamide group, (x) C1 to 4 alkyl sulfonamide a group, (xi) pendant oxy group, (xii) carboxy group, (xiii)-C(O) (O-C1 to 4 alkyl group), (xiv) phosphinyloxy group, (xv)-OP(O) ( O-C1 to 4-alkyl) 2 , (xvi) aminomethyl decyl, (xvii) C1 to 4 alkyl guanylamino and (xviii) C1 to 4 alkyl urethane groups The "C2 to 6 alkynyl group" in the substituent substituted C2 to 6 alkynyl group is ethynyl group, 1-propynyl group, 2-propynyl group, 1-butynyl group, 2-butynyl group, 3-butyl group. Alkynyl, 1-pentynyl, 2-pentynyl, 3-pentynyl, 4-pentynyl, 3-methyl-1-butynyl, 1-hexynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl and 5-hexynyl, and the like.

本發明中，為R2表示之「(1)C1至6烷基、C2至6烯基或C2至6炔基」之取代基之「(iii)-NH(C1至3烷基)及(iv)-N(C1至3烷基)2」中之「C1至3烷基」為甲基、乙基、正丙基及異丙基。又，為-N(C1至3烷基)2時，各個「C1至3烷基」可相同亦可不同。 In the present invention, the substituent of "(1) C1 to 6 alkyl group, C2 to 6 alkenyl group or C2 to 6 alkynyl group" represented by R 2 "(iii)-NH(C1 to 3 alkyl group) and Ic) - "C1 to 3 alkyl" in -N(C1 to 3 alkyl) 2 " is a methyl group, an ethyl group, a n-propyl group and an isopropyl group. Further, when -N(C1 to 3 alkyl) 2 is used, each "C1 to 3 alkyl group" may be the same or different.

本發明中，為R2表示之「(11)C1至4烷基磺醯基」及R2表示之「(1)C1至6烷基、C2至6烯基或C2至6炔基」之取代基之「(viii)C1至4烷基磺醯基」中之「C1至4烷基磺醯基」為甲基磺醯基、乙基磺醯基、正丙基磺醯基、異丙基磺醯基、正 丁基磺醯基、第二丁基磺醯基、第三丁基磺醯基及異丁基磺醯基。 In the present invention, R represents is represented by the sum 22 "(11) C1 to 4 alkylsulfonyl group" and R "(1) C1 to 6 alkyl, C2 to 6 alkenyl or C2 to 6 alkynyl group" of The "C1 to 4-alkylsulfonyl group" in the "(viii) C1 to 4 alkylsulfonyl group" of the substituent is methylsulfonyl, ethylsulfonyl, n-propylsulfonyl, isopropyl Sulfosyl, n-butylsulfonyl, t-butylsulfonyl, tert-butylsulfonyl and isobutylsulfonyl.

本發明中，為R2表示之「(12)磺醯胺基」及R2表示之「(1)C1至6烷基、C2至6烯基或C2至6炔基」之取代基之「(ix)磺醯胺基」中之「磺醯胺基」為-SO2NH2基。 "(1) C1 to 6 alkyl, C2 to 6 alkenyl or C2 to 6 alkynyl group" in the present invention, R 2 is represented by the sum represents 2 "(12) Sulfonic group" and the substituents R 'group of The "sulfonylamino group" in the (ix) sulfonamide group is a -SO 2 NH 2 group.

本發明中，為R2表示之「(13)C1至4烷基磺醯胺基」及R2表示之「(1)C1至6烷基、C2至6烯基或C2至6炔基」之取代基之「(x)C1至4烷基磺醯胺基」中之「C1至4烷基磺醯胺基」表示-SO2NH(C1至4烷基)、-SO2N(C1至4烷基)2、-NHSO2(C1至4烷基)、-N(C1至4烷基)SO2(C1至4烷基)及-N(SO2(C1至4烷基))2，「C1至4烷基磺醯胺基」中之「C1至4烷基」為甲基、乙基、正丙基、異丙基、正丁基、第二丁基、第三丁基及異丁基。又，為-SO2N(C1至4烷基)2、-N(C1至4烷基)SO2(C1至4烷基)及-N(SO2(C1至4烷基))2時，各個「C1至4烷基」可相同亦可不同。 In the present invention, R 2 is represented by the sum represents 2 "(13) C1 to 4 alkylsulfonyl group" and R "(1) C1 to 6 alkyl, C2 to 6 alkenyl or C2 to 6 alkynyl" The "C1 to 4 alkylsulfonylamino group" in the "(x)C1 to 4 alkylsulfonylamino group" of the substituent means -SO 2 NH(C1 to 4 alkyl), -SO 2 N (C1) To 4 alkyl) 2 , -NHSO 2 (C1 to 4 alkyl), -N(C1 to 4 alkyl)SO 2 (C1 to 4 alkyl) and -N(SO 2 (C1 to 4 alkyl)) 2 , "C1 to 4 alkyl" in "C1 to 4 alkylsulfonylamino" is methyl, ethyl, n-propyl, isopropyl, n-butyl, t-butyl, t-butyl And isobutyl. Further, when -SO 2 N(C1 to 4 alkyl) 2 , -N(C1 to 4 alkyl)SO 2 (C1 to 4 alkyl) and -N(SO 2 (C1 to 4 alkyl)) 2 Each "C1 to 4 alkyl group" may be the same or different.

本發明中，為R2表示之「(5)-C(O)(O-C1至4烷基)」及R2表示之「(1)C1至6烷基、C2至6烯基或C2至6炔基」之取代基之「(xiii)-C(O)(O-C1至4烷基)」中之「-C(O)(O-C1至4烷基)」表示羧酸之酯基，具體而言為例如甲酯、乙酯、正丙酯、異丙酯、正丁酯、第二丁酯、第三丁酯及異丁酯基。 In the present invention, it is represented by R 2 and R 2 of the "(5) (O) (O -C1 to C4 alkyl) -C""(1) C1 to 6 alkyl, C2 to 6 alkenyl or C2 "-C(O)(O-C1 to 4 alkyl)" in "(xiii)-C(O)(O-C1 to 4 alkyl)" to a substituent of 6 alkynyl" means a carboxylic acid The ester group is specifically, for example, a methyl ester, an ethyl ester, a n-propyl ester, an isopropyl ester, a n-butyl ester, a second butyl ester, a third butyl ester, and an isobutyl ester group.

本發明中，為R2表示之「(6)膦醯基氧基」及R2表示之「(1)C1至6烷基、C2至6烯基或C2至6炔基」之取代基之「(xiv)膦醯基氧基」中之「膦醯基氧基」為-OP(O)(OH)2基。 "(1) C1 to 6 alkyl, C2 to 6 alkenyl or C2 to 6 alkynyl group" in the present invention, R 2 is represented by the sum represents 2 "(6) phosphino acyl group" and the substituents of R The "phosphonium oxy group" in "(xiv)phosphonium oxy group" is -OP(O)(OH) 2 group.

本發明中，為R2表示之「(7)-OP(O)(O-C1至4烷基)2」及R2表示之「(1)C1至6烷基、C2至6烯基或C2至6炔基」之取代基之「(xv)-OP(O)(O-C1至4烷基)2」中之「-OP(O)(O-C1至4烷 基)2」表示膦酸之酯基，「-OP(O)(O-C1至4烷基)2」中之「C1至4烷基」為甲基、乙基、正丙基、異丙基、正丁基、第二丁基、第三丁基及異丁基，各個「C1至4烷基」可相同亦可不同。 In the present invention, it is represented by R 2 and R 2 of the "(7) (O) (O -C1 to C4 alkyl) 2 -OP""(1) C1 to 6 alkyl, C2 to C6 alkenyl or C2 to 6 alkynyl "the substituent" of the group (xv) -OP (O) ( O-C1 to C4 alkyl) 2 "in the" -OP (O) (O-C1 to C4 alkyl) 2 "means The ester group of phosphonic acid, "C1 to 4 alkyl" in "-OP(O)(O-C1 to 4 alkyl) 2 " is methyl, ethyl, n-propyl, isopropyl, n-butyl The second butyl group, the third butyl group and the isobutyl group may be the same or different in each "C1 to 4 alkyl group".

本發明中，為R2表示之「(15)胺基甲醯基」及R2表示之「(1)C1至6烷基、C2至6烯基或C2至6炔基」之取代基之「(xvi)胺基甲醯基」中之「胺基甲醯基」為-C(O)NH2基。 "(1) C1 to 6 alkyl, C2 to 6 alkenyl or C2 to 6 alkynyl group" in the present invention, R 2 is represented by the sum represents 2 "(15) acyl group A", and the substituent of R The "aminocarbamyl group" in "(xvi)aminomercapto" is a -C(O)NH 2 group.

本發明中，為R2表示之「(16)C1至4烷基醯胺基」及R2表示之「(1)C1至6烷基、C2至6烯基或C2至6炔基」之取代基之「(xvii)C1至4烷基醯胺基」中之「C1至4烷基醯胺基」表示-C(O)NH(C1至4烷基)、-C(O)N(C1至4烷基)2、-NHC(O)(C1至4烷基)、-N(C1至4烷基)C(O)(C1至4烷基)及-N(C(O)(C1至4烷基))2，「C1至4烷基醯胺基」中之「C1至4烷基」為甲基、乙基、正丙基、異丙基、正丁基、第二丁基、第三丁基及異丁基。又，為-C(O)N(C1至4烷基)2、-N(C1至4烷基)C(O)(C1至4烷基)及-N(C(O)(C1至4烷基))2時，各個「C1至4烷基」可相同亦可不同。 "(1) C1 to 6 alkyl, C2 to 6 alkenyl or C2 to 6 alkynyl group" of the present invention, R 2 is represented by the sum represents 2 "(16) C1 to 4 alkyl acyl group" and R The "C1 to 4-alkylguanidino group" in the "(xvii)C1 to 4-alkylammonium group" of the substituent means -C(O)NH(C1 to 4 alkyl), -C(O)N ( C1 to 4 alkyl) 2 , -NHC(O)(C1 to 4 alkyl), -N(C1 to 4 alkyl)C(O)(C1 to 4 alkyl) and -N(C(O)( C1 to 4 alkyl)) 2 , "C1 to 4 alkyl" in "C1 to 4 alkyl guanamine" is methyl, ethyl, n-propyl, isopropyl, n-butyl, second butyl Base, tert-butyl and isobutyl. Further, it is -C(O)N(C1 to 4 alkyl) 2 , -N(C1 to 4 alkyl)C(O)(C1 to 4 alkyl) and -N(C(O)(C1 to 4) In the case of alkyl group)) 2 , each "C1 to 4 alkyl group" may be the same or different.

本發明中，為R2表示之「(17)C1至4烷基胺基甲酸酯基」及R2表示之「(1)C1至6烷基、C2至6烯基或C2至6炔基」之取代基之「(xviii)C1至4烷基胺基甲酸酯基」中之「C1至4烷基胺基甲酸酯基」表示-NHC(O)O(C1至4烷基)、-N(C1至4烷基)C(O)O(C1至4烷基)及-N(C(O)O(C1至4烷基))2，「C1至4烷基胺基甲酸酯基」中之「C1至4烷基」為甲基、乙基、正丙基、異丙基、正丁基、第二丁基、第三丁基及異丁基。又，為-N(C1至4烷基)C(O)O(C1至4烷基)及-N(C(O)O(C1至4烷基))2時，各個「C1 至4烷基」可相同亦可不同。 In the present invention, R 2 is represented by the sum represents 2 "(17) C1 to 4 alkyl carbamates group" and R "(1) C1 to 6 alkyl, C2 to 6 alkenyl or C2 to 6 alkynyl The "C1 to 4 alkyl urethane group" in the "(xviii) C1 to 4 alkyl urethane group" of the substituent of the "base" means -NHC(O)O (C1 to 4 alkyl group) ), -N(C1 to 4 alkyl)C(O)O(C1 to 4 alkyl) and -N(C(O)O(C1 to 4 alkyl)) 2 , "C1 to 4 alkylamino group The "C1 to 4 alkyl group" in the formate group is a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, a second butyl group, a tert-butyl group, and an isobutyl group. Further, when it is -N(C1 to 4 alkyl)C(O)O(C1 to 4 alkyl) and -N(C(O)O(C1 to 4 alkyl)) 2 , each "C1 to 4 alkane" The bases may be the same or different.

本發明中，環Cy2表示之「C3至10單環式碳環或二環式碳環」為例如環丙烷、環丁烷、環戊烷、環己烷、環庚烷、環辛烷、環壬烷、環癸烷、環戊烯、環己烯、環庚烯、環辛烯、環戊二烯、環己二烯、環庚二烯、環辛二烯、苯、戊搭烯、全氫戊搭烯、薁、全氫薁、茚、全氫茚、茚烷、萘、二氫萘、四氫萘及全氫萘環等。 In the present invention, the "C3 to 10 monocyclic carbocyclic ring or bicyclic carbocyclic ring" represented by the ring Cy 2 is, for example, cyclopropane, cyclobutane, cyclopentane, cyclohexane, cycloheptane, cyclooctane, Cyclodecane, cyclodecane, cyclopentene, cyclohexene, cycloheptene, cyclooctene, cyclopentadiene, cyclohexadiene, cycloheptadiene, cyclooctadiene, benzene, pentylene, All hydrogen pentylene, hydrazine, perhydro hydrazine, hydrazine, perhydro hydrazine, decane, naphthalene, dihydronaphthalene, tetrahydronaphthalene, and perhydronaphthalene ring.

本發明中，環Cy2表示之「4至10員單環式雜環或二環式雜環」為例如氧雜環丁烷、氮雜環丁烷、吡咯、咪唑、三唑、四唑、吡唑、吡啶、哌啶、哌、吡、嘧啶、嗒、吖呯、二吖呯、呋喃、吡喃、呯、噻吩、噻喃、噻呯、唑、異唑、噻唑、異噻唑、呋吖、二唑、、二、吖呯、二吖呯、噻二唑、噻、噻二、噻吖呯、噻二吖呯、吲哚、異吲哚、吲哚、苯并呋喃、異苯并呋喃、苯并噻吩、異苯并噻吩、吲唑、喹啉、異喹啉、喹、嘌呤、酞、喋啶、萘啶、喹喔啉、喹唑啉、噌啉、苯并唑、苯并噻唑、苯并咪唑、苯并二茂、苯并硫醇、色烯、苯并呋吖、苯并噻二唑、苯并三唑、吡咯啉、吡咯啶、咪唑啉、咪唑啶、三唑啉、三唑啶、四唑啉、四唑啶、吡唑啉、吡唑啶、二氫吡啶、四氫吡啶、哌啶、二氫吡、四氫吡、哌、二氫嘧啶、四氫嘧啶、全氫嘧啶、二氫嗒、四氫嗒、全氫嗒、二氫吖呯、四氫吖呯、全氫吖呯、二氫二吖呯、四氫二吖呯、全氫二吖呯、二氫呋喃、四氫呋喃、二氫吡喃、四氫吡喃、二氫呯、四氫呯、全氫呯、二氫噻吩、四氫噻吩、二氫噻喃、四氫噻喃、二氫噻呯、四氫噻呯、全氫噻呯、二氫 唑、四氫唑(唑啶)、二氫異唑、四氫異唑(異唑啶)、二氫噻唑、四氫噻唑(噻唑啶)、二氫異噻唑、四氫異噻唑(異噻唑啶)、二氫呋吖、四氫呋吖、二氫二唑、四氫二唑(二唑啶)、二氫、四氫、二氫二、四氫二、二氫吖呯、四氫吖呯、全氫吖呯、二氫二吖呯、四氫二吖呯、全氫二吖呯、二氫噻二唑、四氫噻二唑(噻二唑啶)、二氫噻、四氫噻、二氫噻二、四氫噻二、二氫噻吖呯、四氫噻吖呯、全氫噻吖呯、二氫噻二吖呯、四氫噻二吖呯、全氫噻二吖呯、嗎啉、硫代嗎啉、噻仙、吲哚啉、異吲哚啉、二氫苯并呋喃、全氫苯并呋喃、二氫異苯并呋喃、全氫異苯并呋喃、二氫苯并噻吩、全氫苯并噻吩、二氫異苯并噻吩、全氫異苯并噻吩、二氫吲唑、全氫吲唑、二氫喹啉、四氫喹啉、全氫喹啉、二氫異喹啉、四氫異喹啉、全氫異喹啉、二氫酞、四氫酞、全氫酞、二氫萘啶、四氫萘啶、全氫萘啶、二氫喹喔啉、四氫喹喔啉、全氫喹喔啉、二氫喹唑啉、四氫喹唑啉、全氫喹唑啉、二氫噌啉、四氫噌啉、全氫噌啉、苯并噻仙、二氫苯并、二氫苯并噻、吡嗎啉、二氫苯并唑、全氫苯并唑、二氫苯并噻唑、全氫苯并噻唑、二氫苯并咪唑、全氫苯并咪唑、二戊烷、二烷、二茚烷、苯并二烷、硫代色滿、二氫苯并二英、二氫苯并氧硫雜環己二烯、吡啶酮及色滿環等。 In the present invention, the "C4" to "monocyclic heterocyclic ring or bicyclic heterocyclic ring" represented by the ring Cy 2 is, for example, oxetane, azetidine, pyrrole, imidazole, triazole, tetrazole, Pyrazole, pyridine, piperidine, piperazine Pyr Pyrimidine , hydrazine, diterpenes, furan, pyran, Ruthenium, thiophene, thiopyran, thiazide, Azole Oxazole, thiazole, isothiazole, furazan, Diazole, , two , Oh, Diterpenoid, thiadiazole, thiophene Thia , thiazide, thiazepine, hydrazine, isoindole, hydrazine , benzofuran, isobenzofuran, benzothiophene, isobenzothiophene, carbazole, quinoline, isoquinoline, quin , 嘌呤, 酞 , acridine, naphthyridine, quinoxaline, quinazoline, porphyrin, benzo Oxazole, benzothiazole, benzimidazole, benzodiazepine Mao, benzo Mercaptan, chromene, benzofurazan, benzothiadiazole, benzotriazole, pyrroline, pyrrolidine, imidazoline, imidazolium, triazoline, triazole, tetrazoline, tetrazolidine, Pyrazoline, pyrazolidine, dihydropyridine, tetrahydropyridine, piperidine, dihydropyridyl Tetrahydropyridyl Piper , dihydropyrimidine, tetrahydropyrimidine, perhydropyrimidine, indoline Tetrahydroanthraquinone All hydroquinone , indoline, tetrahydroanthracene, perhydroanthraquinone, dihydroindrene, tetrahydrofuran, perhydrodifluorene, dihydrofuran, tetrahydrofuran, dihydropyran, tetrahydropyran, Dihydrogen Helium, tetrahydrogen Helium, all hydrogen Anthracene, dihydrothiophene, tetrahydrothiophene, dihydrothiopyran, tetrahydrothiopyran, dihydrothiazide, tetrahydrothiazolidine, perhydrothiazolidine, dihydrogen Oxazole, tetrahydrogen Azole Oxazolidine) Azole, tetrahydroiso Azole Zolidine, dihydrothiazole, tetrahydrothiazole (thiazolidine), dihydroisothiazole, tetrahydroisothiazole (isothiazolidine), dihydrofurazan, tetrahydrofurazan, dihydrogen Diazole, tetrahydrogen Diazole Diazolidine), dihydrogen Tetrahydrogen Dihydrogen two Tetrahydrogen two Dihydrogen Helium, tetrahydrogen Helium, all hydrogen Helium, dihydrogen Diterpene, tetrahydrogen Diterpene, all hydrogen Diterpene, dihydrothiadiazole, tetrahydrothiadiazole (thiadiazolidine), dihydrothiazide Tetrahydrothiazide Dihydrothiazide Tetrahydrothiazide , dihydrothiazide, tetrahydrothiazide, perhydrothiazolidine, dihydrothiadiazine, tetrahydrothiadiazine, perhydrothiadiazine, morpholine, thiomorpholine, Thiamine, porphyrin, isoporphyrin, dihydrobenzofuran, perhydrobenzofuran, dihydroisobenzofuran, perhydroisobenzofuran, dihydrobenzothiophene, perhydrobenzothiophene, Dihydroisobenzothiophene, perhydroisobenzothiophene, dihydrocarbazole, perhydrocarbazole, dihydroquinoline, tetrahydroquinoline, perhydroquinoline, dihydroisoquinoline, tetrahydroisoquinoline , perhydroisoquinoline, indoline Tetrahydroanthraquinone All hydroquinone , dihydronaphthyridine, tetrahydronaphthyridine, perhydronaphthyridine, dihydroquinoxaline, tetrahydroquinoxaline, perhydroquinoxaline, dihydroquinazoline, tetrahydroquinazoline, perhydroquinazoline Porphyrin, dihydroporphyrin, tetrahydroporphyrin, perhydroporphyrin, benzo Thioxan, dihydrobenzo Dihydrobenzothiazide Pyr Morpholine, dihydrobenzo Oxazole, all hydrogen benzo Azole, dihydrobenzothiazole, perhydrobenzothiazole, dihydrobenzimidazole, perhydrobenzimidazole, two Pentane, two Alkane, two Decane, benzoic acid Alkane, thiochroman, dihydrobenzo English, dihydrobenzoxylene thicyclohexadiene, pyridone and color ring.

本發明中，R6表示之「可經選自由(i)鹵素原子、(ii)羥基、(iii)側氧基、(iv)-NH(C1至3烷基)、(v)-N(C1至3烷基)2、(vi)C1至6烷氧基、(vii)胺基、(viii)氰基、(ix)硝基、(x)C1至4烷基磺醯基、(xi)磺醯胺基、(xii)C1至4烷基磺醯胺基、(xiii)羧基、 (xiv)-C(O)(O-C1至4烷基)、(xv)膦醯基氧基、(xvi)-OP(O)(O-C1至4烷基)2、(xvii)胺基甲醯基、(xviii)C1至4烷基醯胺基及(xix)C1至4烷基胺基甲酸酯基所成群組之取代基取代之C1至6烷基」中之「C1至6烷基」與上述R1表示之「可經鹵素原子或側氧基取代之C1至6烷基」中之「C1至6烷基」同意義。 In the present invention, R 6 means "may be selected from (i) a halogen atom, (ii) a hydroxyl group, (iii) a pendant oxy group, (iv) -NH (C1 to 3 alkyl group), (v)-N ( C1 to 3 alkyl) 2 , (vi) C1 to 6 alkoxy, (vii) amine, (viii) cyano, (ix) nitro, (x) C1 to 4 alkylsulfonyl, (xi Sulfonamide, (xii) C1 to 4 alkylsulfonylamino, (xiii) carboxyl, (xiv)-C(O)(O-C1 to 4 alkyl), (xv) phosphinyloxy , (xvi)-OP(O)(O-C1 to 4 alkyl) 2 , (xvii) aminomethyl decyl, (xviii) C1 to 4 alkyl guanylamino and (xix) C1 to 4 alkylamine a "C1 to 6 alkyl group" in the C1 to 6 alkyl group substituted by a substituent of a group of a carboxylic acid group, and a C1 to 6 alkyl group which may be substituted by a halogen atom or a pendant oxy group as represented by the above R 1 The "C1 to 6 alkyl group" in the "base" has the same meaning.

本發明中，R6表示之「可經選自由(i)鹵素原子、(ii)羥基、(iii)側氧基、(iv)-NH(C1至3烷基)、(v)-N(C1至3烷基)2、(vi)C1至6烷氧基、(vii)胺基、(viii)氰基、(ix)硝基、(x)C1至4烷基磺醯基、(xi)磺醯胺基、(xii)C1至4烷基磺醯胺基、(xiii)羧基、(xiv)-C(O)(O-C1至4烷基)、(xv)膦醯基氧基、(xvi)-OP(O)(O-C1至4烷基)2、(xvii)胺基甲醯基、(xviii)C1至4烷基醯胺基及(xix)C1至4烷基胺基甲酸酯基所成群組之取代基取代之C2至6烯基」中之「C2至6烯基」與上述R2表示之「C2至6烯基」同意義。 In the present invention, R 6 means "may be selected from (i) a halogen atom, (ii) a hydroxyl group, (iii) a pendant oxy group, (iv) -NH (C1 to 3 alkyl group), (v)-N ( C1 to 3 alkyl) 2 , (vi) C1 to 6 alkoxy, (vii) amine, (viii) cyano, (ix) nitro, (x) C1 to 4 alkylsulfonyl, (xi Sulfonamide, (xii) C1 to 4 alkylsulfonylamino, (xiii) carboxyl, (xiv)-C(O)(O-C1 to 4 alkyl), (xv) phosphinyloxy , (xvi)-OP(O)(O-C1 to 4 alkyl) 2 , (xvii) aminomethyl decyl, (xviii) C1 to 4 alkyl guanylamino and (xix) C1 to 4 alkylamine The "C2 to 6 alkenyl group" in the C2 to 6 alkenyl group substituted by the substituent of the group of the carbamate groups has the same meaning as the "C2 to 6 alkenyl group" represented by the above R 2 .

本發明中，R6表示之「可經選自由(i)鹵素原子、(ii)羥基、(iii)側氧基、(iv)-NH(C1至3烷基)、(v)-N(C1至3烷基)2、(vi)C1至6烷氧基、(vii)胺基、(viii)氰基、(ix)硝基、(x)C1至4烷基磺醯基、(xi)磺醯胺基、(xii)C1至4烷基磺醯胺基、(xiii)羧基、(xiv)-C(O)(O-C1至4烷基)、(xv)膦醯基氧基、(xvi)-OP(O)(O-C1至4烷基)2、(xvii)胺基甲醯基、(xviii)C1至4烷基醯胺基及(xix)C1至4烷基胺基甲酸酯基所成群組之取代基取代之C2至6炔基」中之「C2至6炔基」與上述R2表示之「C2至6炔基」同意義。 In the present invention, R 6 means "may be selected from (i) a halogen atom, (ii) a hydroxyl group, (iii) a pendant oxy group, (iv) -NH (C1 to 3 alkyl group), (v)-N ( C1 to 3 alkyl) 2 , (vi) C1 to 6 alkoxy, (vii) amine, (viii) cyano, (ix) nitro, (x) C1 to 4 alkylsulfonyl, (xi Sulfonamide, (xii) C1 to 4 alkylsulfonylamino, (xiii) carboxyl, (xiv)-C(O)(O-C1 to 4 alkyl), (xv) phosphinyloxy , (xvi)-OP(O)(O-C1 to 4 alkyl) 2 , (xvii) aminomethyl decyl, (xviii) C1 to 4 alkyl guanylamino and (xix) C1 to 4 alkylamine The "C2 to 6 alkynyl group" in the C2 to 6 alkynyl group substituted by the substituent of the group of the carbamate groups has the same meaning as the "C2 to 6 alkynyl group" represented by the above R 2 .

本發明中，R6表示之「可經選自由(i)鹵素原子、(ii)羥基、(iii)側氧基、(iv)-NH(C1至3烷基)、(v)-N(C1至3烷基)2、(vi)C1至6烷氧基、(vii)胺基、(viii)氰基、(ix)硝基、(x)C1至4烷 基磺醯基、(xi)磺醯胺基、(xii)C1至4烷基磺醯胺基、(xiii)羧基、(xiv)-C(O)(O-C1至4烷基)、(xv)膦醯基氧基、(xvi)-OP(O)(O-C1至4烷基)2、(xvii)胺基甲醯基、(xviii)C1至4烷基醯胺基及(xix)C1至4烷基胺基甲酸酯基所成群組之取代基取代之C3至6環烷基」中之「C3至6環烷基」與上述R1表示之「可經鹵素原子或C1至3烷基取代之C3至6環烷基」中之「C3至6環烷基」同意義。 In the present invention, R 6 means "may be selected from (i) a halogen atom, (ii) a hydroxyl group, (iii) a pendant oxy group, (iv) -NH (C1 to 3 alkyl group), (v)-N ( C1 to 3 alkyl) 2 , (vi) C1 to 6 alkoxy, (vii) amine, (viii) cyano, (ix) nitro, (x) C1 to 4 alkylsulfonyl, (xi Sulfonamide, (xii) C1 to 4 alkylsulfonylamino, (xiii) carboxyl, (xiv)-C(O)(O-C1 to 4 alkyl), (xv) phosphinyloxy , (xvi)-OP(O)(O-C1 to 4 alkyl) 2 , (xvii) aminomethyl decyl, (xviii) C1 to 4 alkyl guanylamino and (xix) C1 to 4 alkylamine "C3 to 6 cycloalkyl group" in the C3 to 6 cycloalkyl group substituted by a substituent of a group of a carbamate group, and the above R 1 represents "may be substituted by a halogen atom or a C1 to 3 alkyl group" The "C3 to 6 cycloalkyl group" in the C3 to 6 cycloalkyl group has the same meaning.

本發明中，為R6表示之「(1)C1至6烷基、C2至6烯基、C2至6炔基或C3至6環烷基」之取代基之「(iv)-NH(C1至3烷基)及(v)-N(C1至3烷基)2」及R6表示之「(8)-NH(C1至3烷基)及(9)-N(C1至3烷基)2」中之「-NH(C1至3烷基)及-N(C1至3烷基)2」之「C1至3烷基」為甲基、乙基、正丙基及異丙基。又，為-N(C1至3烷基)2時，各個「C1至3烷基」可相同亦可不同。 In the present invention, the substituent of "(1) C1 to 6 alkyl group, C2 to 6 alkenyl group, C2 to 6 alkynyl group or C3 to 6 cycloalkyl group" represented by R 6 "(iv)-NH(C1) "(8)-NH(C1 to 3 alkyl) and (9)-N (C1 to 3 alkyl)" to "3 alkyl) and (v)-N(C1 to 3 alkyl) 2 " and R 6 ) 2 "in the" -NH (C1 to C3 alkyl) and -N (C1 to C3 alkyl) "2" of the C1 to 3 alkyl "is methyl, ethyl, n-propyl and isopropyl. Further, when -N(C1 to 3 alkyl) 2 is used, each "C1 to 3 alkyl group" may be the same or different.

本發明中，為R6表示之「(1)C1至6烷基、C2至6烯基、C2至6炔基或C3至6環烷基」之取代基之「(vi)C1至6烷氧基」中之「C1至6烷氧基」為例如甲氧基、乙氧基、丙氧基、異丙氧基、丁氧基、1-甲基丙氧基、第三丁氧基、異丁氧基、戊基氧基、1-甲基丁氧基、2-甲基丁氧基、3-甲基丁氧基、1，1-二甲基丙氧基、1，2-二甲基丙氧基、2，2-二甲基丙氧基、己基氧基、1-甲基戊基氧基、2-甲基戊基氧基、3-甲基戊基氧基、4-甲基戊基氧基、1，1-二甲基丁氧基、1，2-二甲基丁氧基、1，3-二甲基丁氧基、1-甲基-1-乙基丙氧基、1-甲基-2-乙基丙氧基、1，2-二甲基丁氧基、2，2-二甲基丁氧基、1-乙基-2-甲基丙氧基、2-乙基-2-甲基丙氧基及1-乙基丁氧基等。 In the present invention, is R 6 represents the "(1) C1 to 6 alkyl, C2 to 6 alkenyl, C2 to C6 alkynyl or C3 to 6 cycloalkyl" the substituent "of the group (vi) C1 to 6 alkoxy The "C1 to 6 alkoxy group" in the oxy group is, for example, a methoxy group, an ethoxy group, a propoxy group, an isopropoxy group, a butoxy group, a 1-methylpropoxy group, a third butoxy group, Isobutoxy, pentyloxy, 1-methylbutoxy, 2-methylbutoxy, 3-methylbutoxy, 1,1-dimethylpropoxy, 1,2-di Methylpropoxy, 2,2-dimethylpropoxy, hexyloxy, 1-methylpentyloxy, 2-methylpentyloxy, 3-methylpentyloxy, 4- Methylpentyloxy, 1,1-dimethylbutoxy, 1,2-dimethylbutoxy, 1,3-dimethylbutoxy, 1-methyl-1-ethylpropane Oxyl, 1-methyl-2-ethylpropoxy, 1,2-dimethylbutoxy, 2,2-dimethylbutoxy, 1-ethyl-2-methylpropoxy , 2-ethyl-2-methylpropoxy and 1-ethylbutoxy and the like.

本發明中，為R6表示之「(18)C1至4烷基磺醯基」 及R6表示之「(1)C1至6烷基、C2至6烯基、C2至6炔基或C3至6環烷基」之取代基之「(x)C1至4烷基磺醯基」中之「C1至4烷基磺醯基」與上述R2表示之「(11)C1至4烷基磺醯基」中之「C1至4烷基磺醯基」同意義。 In the present invention, R 6 is represented by the "(18) C1 to 4 alkylsulfonyl group", and R 6 represents the "(1) C1 to 6 alkyl, C2 to 6 alkenyl, C2 to C6 alkynyl or C3 "C1 to 4 alkylsulfonyl" in "(x)C1 to 4 alkylsulfonyl" to a substituent of 6-cycloalkyl" and "(11)C1 to 4 alkyl represented by the above R 2 "C1 to 4 alkylsulfonyl" in the sulfonyl group has the same meaning.

本發明中，為R6表示之「(19)C1至4烷基磺醯胺基」及R6表示之「(1)C1至6烷基、C2至6烯基、C2至6炔基或C3至6環烷基」之取代基之「(xii)C1至4烷基磺醯胺基」中之「C1至4烷基磺醯胺基」與上述R2表示之「(13)C1至4烷基磺醯胺基」中之「C1至4烷基磺醯胺基」同意義。 In the present invention, R 6 is represented by the "(19) C1 to 4 alkylsulfonyl group", and R 6 represents the "(1) C1 to 6 alkyl, C2 to 6 alkenyl, C2 to 6 alkynyl, or a C3 to 6 cycloalkyl "the substituent" of the group (XII) C1 to 4 alkylsulfonyl group "in the" C1 to 4 alkylsulfonyl group "represented by R 2 of the above-described" (13 is) C1 to The "C1 to 4-alkylsulfonylamino group" in the 4-alkylsulfonylamino group has the same meaning.

本發明中，為R6表示之「(11)-C(O)(O-C1至4烷基)」及R6表示之「(1)C1至6烷基、C2至6烯基、C2至6炔基或C3至6環烷基」之取代基之「(xiv)-C(O)(O-C1至4烷基)」中之「-C(O)(O-C1至4烷基)」與上述R2表示之「(5)-C(O)(O-C1至4烷基)」中之「-C(O)(O-C1至4烷基)」同意義。 In the present invention, R 6 is represented by the "(11) -C (O) ( O-C1 to C4 alkyl)", and R 6 represents the "(1) C1 to 6 alkyl, C2 to 6 alkenyl, C2 "-C(O)(O-C1 to 4) in "(xiv)-C(O)(O-C1 to 4 alkyl)" to a substituent of 6 alkynyl or C3 to 6 cycloalkyl"")) has the same meaning as "-C(O)(O-C1 to 4 alkyl)" in "(5)-C(O)(O-C1 to 4 alkyl)" represented by the above R 2 .

本發明中，為R6表示之「(12)胺基甲醯基」及R6表示之「(1)C1至6烷基、C2至6烯基、C2至6炔基或C3至6環烷基」之取代基之「(xvii)胺基甲醯基」中之「胺基甲醯基」為-C(O)NH2基。 In the present invention, R 6 is represented by the "(12) acyl group A", and R 6 represents the "(1) C1 to 6 alkyl, C2 to 6 alkenyl, C2 to C6 alkynyl or C3 to 6 cycloalkyl The "aminocarbamoyl group" in the "(xvii)aminomercapto group" of the substituent of the alkyl group is a -C(O)NH 2 group.

本發明中，為R6表示之「(13)C1至4烷基醯胺基」及R6表示之「(1)C1至6烷基、C2至6烯基、C2至6炔基或C3至6環烷基」之取代基之「(xviii)C1至4烷基醯胺基」中之「C1至4烷基醯胺基」與上述R2表示之「(16)C1至4烷基醯胺基」中之「C1至4烷基醯胺基」同意義。 In the present invention, R 6 is represented by the "(13) C1 to 4 alkyl acyl group", and R 6 represents the "(1) C1 to 6 alkyl, C2 to 6 alkenyl, C2 to C6 alkynyl or C3 "C1 to 4 alkyl guanamine group" in "(xviii) C1 to 4 alkyl guanylamino group" to a substituent of 6 cycloalkyl" and "16) C1 to 4 alkyl represented by the above R 2 The "C1 to 4 alkyl guanamine group" in the amide group has the same meaning.

本發明中，為R6表示之「(20)C1至4烷基胺基甲酸 酯基」及R6表示之「(1)C1至6烷基、C2至6烯基、C2至6炔基或C3至6環烷基」之取代基之「(xix)C1至4烷基胺基甲酸酯基」中之「C1至4烷基胺基甲酸酯基」與上述R2表示之「(17)C1至4烷基胺基甲酸酯基」中之「C1至4烷基胺基甲酸酯基」同意義。 In the present invention, R 6 is represented by the "(20) C1 to 4 alkyl carbamates group" and R 6 represents the "(1) C1 to 6 alkyl, C2 to 6 alkenyl, C2 to 6 alkynyl "C1 to 4 alkyl urethane group" in the "(xix) C1 to 4 alkyl urethane group" of the substituent of the group or C3 to 6 cycloalkyl" and the above R 2 The "C1 to 4 alkyl urethane group" in "(17) C1 to 4 alkyl urethane group" has the same meaning.

本發明中，R6表示之「(3)C1至4烷氧基」中之「C1至4烷氧基」為例如甲氧基、乙氧基、丙氧基、異丙氧基、丁氧基、1-甲基丙氧基、第三丁氧基、異丁氧基等。 In the present invention, the "C1 to 4 alkoxy group" in the "(3) C1 to 4 alkoxy group" represented by R 6 is, for example, a methoxy group, an ethoxy group, a propoxy group, an isopropoxy group or a butoxy group. Base, 1-methylpropoxy, tert-butoxy, isobutoxy and the like.

本發明中，為R6表示之「(4)膦醯基氧基」及R6表示之「(1)C1至6烷基、C2至6烯基、C2至6炔基或C3至6環烷基」之取代基之「(xv)膦醯基氧基」中之「膦醯基氧基」為-OP(O)(OH)2基。 In the present invention, R 6 is represented by the "(4) phosphonate acyl group" and R 6 represents the "(1) C1 to 6 alkyl, C2 to 6 alkenyl, C2 to C6 alkynyl or C3 to 6 cycloalkyl The "phosphonium oxy group" in the "(xv)phosphinyloxy group" of the substituent of the alkyl group is -OP(O)(OH) 2 group.

本發明中，為R6表示之「(5)-OP(O)(O-C1至4烷基)2」及R6表示之「(1)C1至6烷基、C2至6烯基、C2至6炔基或C3至6環烷基」之取代基之「(xvi)-OP(O)(O-C1至4烷基)2」中之「-OP(O)(O-C1至4烷基)2」表示膦酸之酯基，「-OP(O)(O-C1至4烷基)2」中之「C1至4烷基」為甲基、乙基、正丙基、異丙基、正丁基、第二丁基、第三丁基及異丁基，各個「C1至4烷基」可相同亦可不同。 In the present invention, R 6 is represented by the "(5) -OP (O) ( O-C1 to C4 alkyl) 2", and R 6 represents the "(1) C1 to 6 alkyl, C2 to C6 alkenyl, "-OP(O)(O-C1 to "(xvi)-OP(O)(O-C1 to 4 alkyl) 2 ") of a substituent of C2 to 6 alkynyl or C3 to 6 cycloalkyl" 4 alkyl) 2 ′′ represents an ester group of a phosphonic acid, and “C1 to 4 alkyl” in “-OP(O)(O-C1 to 4 alkyl) 2 ” is methyl, ethyl, n-propyl, Isopropyl, n-butyl, t-butyl, tert-butyl and isobutyl, each "C1 to 4-alkyl" may be the same or different.

本發明中，為R6表示之「(6)磺醯胺基」及R6表示之「(1)C1至6烷基、C2至6烯基、C2至6炔基或C3至6環烷基」之取代基之「(xi)磺醯胺基」中之「磺醯胺基」為-SO2NH2基。 In the present invention, as represented by the R 6 "(6) Sulfonic group" and R 6 represents the "(1) C1 to 6 alkyl, C2 to 6 alkenyl, C2 to C6 alkynyl or C3 to 6 cycloalkyl The "sulfonylamino group" in the "(xi) sulfonamide group" of the substituent of the group is -SO 2 NH 2 group.

本發明中，R3表示之「可經鹵素原子取代之C1至3烷基」中之「C1至3烷基」與上述R1表示之「可經鹵素原子或C1至3烷基取代之C3至6環烷基」中之「C1至3烷基」同意義。 In the present invention, R 3 represents "C1 to 3 alkyl group" in "C1 to 3 alkyl group which may be substituted by a halogen atom" and "C3 which may be substituted by a halogen atom or a C1 to 3 alkyl group" represented by the above R 1 The "C1 to 3 alkyl group" in the 6-cycloalkyl group has the same meaning.

本發明中，R3表示之「可經鹵素原子取代之C1至3烷氧基」中之「C1至3烷氧基」為甲氧基、乙氧基、丙氧基及異丙氧基。 In the present invention, the "C1 to 3 alkoxy group" in the "C1 to 3 alkoxy group which may be substituted by a halogen atom" represented by R 3 is a methoxy group, an ethoxy group, a propoxy group and an isopropoxy group.

本發明中，R4表示之「可經鹵素原子取代之C1至3烷基」中之「C1至3烷基」與上述R1表示之「可經鹵素原子或C1至3烷基取代之C3至6環烷基」中之「C1至3烷基」同意義。 In the present invention, R 4 represents "C1 to 3 alkyl group" in the "C1 to 3 alkyl group which may be substituted by a halogen atom" and "C3 which may be substituted by a halogen atom or a C1 to 3 alkyl group" represented by the above R 1 The "C1 to 3 alkyl group" in the 6-cycloalkyl group has the same meaning.

本發明中，R4表示之「可經鹵素原子取代之C1至3烷氧基」中之「C1至3烷氧基」與上述R3表示之「可經鹵素原子取代之C1至3烷氧基」中之「C1至3烷氧基」同意義。 In the present invention, R 4 represents "C1 to 3 alkoxy group" in the "C1 to 3 alkoxy group which may be substituted by a halogen atom" and "the C1 to 3 alkoxy group which may be substituted by a halogen atom" represented by the above R 3 The "C1 to 3 alkoxy group" in the "base" has the same meaning.

本發明中，Y表示之「可經氧化之硫原子」表示「硫原子」及「經氧化之硫原子」，「經氧化之硫原子」表示亞碸基(-SO-)及磺醯基(-SO2-)。 In the present invention, the term "oxidizable sulfur atom" denotes "sulfur atom" and "oxidized sulfur atom", and "oxidized sulfur atom" means anthracene group (-SO-) and sulfonyl group ( -SO 2 -).

本發明中，Z表示之「形成 In the present invention, Z represents "formation"

環之碳原子以氧原子取代之基」為形成該環之1個亞甲基(-CH2-)以氧原子(-O-)取代之基，例如下述環等。 The group in which the carbon atom of the ring is substituted with an oxygen atom is a group in which one methylene group (-CH2-) forming the ring is substituted with an oxygen atom (-O-), for example, the following ring or the like.

本發明中，R5表示之「可經羥基取代之C1至4烷基」中之「C1至4烷基」為甲基、乙基、正丙基、異丙基、正丁基、第二丁基、第三丁基及異丁基。 In the present invention, the "C1 to 4 alkyl group" in the "C1 to 4 alkyl group which may be substituted by a hydroxyl group" represented by R 5 is a methyl group, an ethyl group, a n-propyl group, an isopropyl group, an n-butyl group, and a second group. Butyl, tert-butyl and isobutyl.

本發明中，R7表示之「(1)C1至6烷基、C3至6環烷基、C1至6烷基之碳原子以氧原子取代之基或C3至6環烷基之碳原子以氧原子取代之基」中之「C1至6烷基」與上述R1表示之「可經鹵素原子或側氧基取代之C1至6烷基」中之「C1至6烷基」同意義。 In the present invention, R 7 represents "(1) a C1 to 6 alkyl group, a C3 to 6 cycloalkyl group, a C1 to 6 alkyl group having a carbon atom substituted with an oxygen atom or a C3 to 6 cycloalkyl group as a carbon atom. an oxygen atom substituted with the group "in the" C1 to C6 alkyl "of the above-described R 1 represents" may be substituted by a halogen atom or a side of a C1 to C6 alkyl group "in the" C1 to 6 alkyl "meaning the same.

本發明中，R7表示之「(1)C1至6烷基、C3至6環烷基、C1至6烷基之碳原子以氧原子取代之基或C3至6環烷基之碳原子以氧原子取代之基」中之「C1至6烷基之碳原子以氧原子取代之基」為該C1至6烷基之1個亞甲基(-CH2-)以氧原子(-O-)取代之基，為例如羥基、甲氧基、羥基甲基、乙氧基、甲氧基甲基、2-羥基乙基、1-羥基乙基、2-羥基丙基、異丙氧基、1-甲基-2-羥基乙基、1-甲氧基乙基、1-羥基丙基、1-羥基-1-甲基乙基、丁氧基、丙氧基甲基、2-乙氧基乙基、3-甲氧基丙基、1-乙氧基乙基、 1-甲氧基丙烷-2-基、第二丁氧基、2-甲氧基丙基、異丁氧基、異丙氧基甲基、1-羥基-1-甲基丙基、2-羥基-1-甲基丙基及2-羥基2-甲基丙基等。 In the present invention, R 7 represents "(1) a C1 to 6 alkyl group, a C3 to 6 cycloalkyl group, a C1 to 6 alkyl group having a carbon atom substituted with an oxygen atom or a C3 to 6 cycloalkyl group as a carbon atom. The "C1 to 6 alkyl group in which the carbon atom is substituted with an oxygen atom" in the "oxygen atom-substituted group" is a methylene group (-CH2-) of the C1 to 6 alkyl group as an oxygen atom (-O-). Substituents such as hydroxy, methoxy, hydroxymethyl, ethoxy, methoxymethyl, 2-hydroxyethyl, 1-hydroxyethyl, 2-hydroxypropyl, isopropoxy, 1 -methyl-2-hydroxyethyl, 1-methoxyethyl, 1-hydroxypropyl, 1-hydroxy-1-methylethyl, butoxy, propoxymethyl, 2-ethoxy Ethyl, 3-methoxypropyl, 1-ethoxyethyl, 1-methoxypropan-2-yl, second butoxy, 2-methoxypropyl, isobutoxy, iso Propyloxymethyl, 1-hydroxy-1-methylpropyl, 2-hydroxy-1-methylpropyl and 2-hydroxy 2-methylpropyl, and the like.

本發明中，為R7表示之「(1)C1至6烷基、C3至6環烷基、C1至6烷基之碳原子以氧原子取代之基或C3至6環烷基之碳原子以氧原子取代之基」及R7表示之「(1)C1至6烷基、C3至6環烷基、C1至6烷基之碳原子以氧原子取代之基或C3至6環烷基之碳原子以氧原子取代之基」之取代基之「(ii)C3至6環烷基」中之「C3至6環烷基」與上述R1表示之「可經鹵素原子或C1至3烷基取代之C3至6環烷基」中之「C3至6環烷基」同意義。 In the present invention, is R "(1) C1 to 6 alkyl, C3 to 6 cycloalkyl of 7 indicates, a C1 to 6 carbon atoms, a substituted alkyl group of an oxygen atom of the group or a cycloalkyl group of C3 to 6 carbon atoms, "Substituents substituted with an oxygen atom" and R 7 represent "(1) a C1 to 6 alkyl group, a C3 to 6 cycloalkyl group, a C1 to 6 alkyl group having a carbon atom substituted with an oxygen atom or a C3 to 6 cycloalkyl group. The "C3 to 6 cycloalkyl group" in the "(ii) C3 to 6 cycloalkyl group" of the substituent of the carbon atom substituted with an oxygen atom" and the above R 1 "may pass through a halogen atom or C1 to 3" The "C3 to 6 cycloalkyl group" in the alkyl substituted C3 to 6 cycloalkyl group has the same meaning.

本發明中，R7表示之「(1)C1至6烷基、C3至6環烷基、C1至6烷基之碳原子以氧原子取代之基或C3至6環烷基之碳原子以氧原子取代之基」中之「C3至6環烷基之碳原子以氧原子取代之基」為例如該C3至6環烷基之1個亞甲基(-CH2-)以氧原子(-O-)取代之基，為環氧乙基、1-氧雜環丁烷基、2-氧雜環丁烷基、1-四氫呋喃基、2-四氫呋喃基、1-四氫-2H-吡喃基、2-四氫-2H-吡喃基及3-四氫-2H-吡喃基等。 In the present invention, R 7 represents "(1) a C1 to 6 alkyl group, a C3 to 6 cycloalkyl group, a C1 to 6 alkyl group having a carbon atom substituted with an oxygen atom or a C3 to 6 cycloalkyl group as a carbon atom. The "C3 to 6 cycloalkyl group in which the carbon atom is substituted with an oxygen atom" in the "oxygen atom-substituted group" is, for example, a methylene group (-CH2-) of the C3 to 6 cycloalkyl group as an oxygen atom (- O-) substituted group, epoxy ethyl, 1-oxetanyl, 2-oxetanyl, 1-tetrahydrofuranyl, 2-tetrahydrofuranyl, 1-tetrahydro-2H-pyran Base, 2-tetrahydro-2H-pyranyl and 3-tetrahydro-2H-pyranyl and the like.

本發明中，為R7表示之「(1)C1至6烷基、C3至6環烷基、C1至6烷基之碳原子以氧原子取代之基或C3至6環烷基之碳原子以氧原子取代之基」之取代基之「(v)4至6員單環式雜環」中之「4至6員單環式雜環」為氧雜環丁烷、硫雜環丁烷、氮雜環丁烷、吡咯、咪唑、三唑、四唑、吡唑、吡啶、哌啶、哌、吡、嘧啶、嗒、呋喃、吡喃、噻吩、噻喃、唑、異 唑、噻唑、異噻唑、呋吖、二唑、、二、噻二唑、噻、噻二、吡咯啉、吡咯啶、咪唑啉、咪唑啶、三唑啉、三唑啶、四唑啉、四唑啶、吡唑啉、吡唑啶、二氫吡啶、四氫吡啶、二氫吡、四氫吡、二氫嘧啶、四氫嘧啶、全氫嘧啶、二氫嗒、四氫嗒、全氫嗒、二氫呋喃、四氫呋喃、二氫吡喃、四氫吡喃、二氫噻吩、四氫噻吩、二氫噻喃、四氫噻喃、二氫唑、四氫唑(唑啶)、二氫異唑、四氫異唑(異唑啶)、二氫噻唑、四氫噻唑(噻唑啶)、二氫異噻唑、四氫異噻唑(異噻唑啶)、二氫呋吖、四氫呋吖、二氫二唑、四氫二唑(二唑啶)、二氫、四氫、二氫二、四氫二、二氫噻二唑、四氫噻二唑(噻二唑啶)、二氫噻、四氫噻、二氫噻二、四氫噻二、嗎啉、硫代嗎啉、環丁烷及噻仙環等。 In the present invention, is R "(1) C1 to 6 alkyl, C3 to 6 cycloalkyl of 7 indicates, a C1 to 6 carbon atoms, a substituted alkyl group of an oxygen atom of the group or a cycloalkyl group of C3 to 6 carbon atoms, The "4 to 6 member monocyclic heterocyclic ring" in the "(v) 4 to 6 membered monocyclic heterocyclic ring" of the substituent substituted by an oxygen atom is oxetane or thietane. , azetidine, pyrrole, imidazole, triazole, tetrazole, pyrazole, pyridine, piperidine, piperazine Pyr Pyrimidine , furan, pyran, thiophene, thiopyran, Azole Oxazole, thiazole, isothiazole, furazan, Diazole, , two Thiadiazole, thiadipine Thia , pyrroline, pyrrolidine, imidazoline, imidazolidinium, triazoline, triazopyridine, tetrazololine, tetrazoleidine, pyrazoline, pyrazolidine, dihydropyridine, tetrahydropyridine, dihydropyridyl Tetrahydropyridyl , dihydropyrimidine, tetrahydropyrimidine, perhydropyrimidine, indoline Tetrahydroanthraquinone All hydroquinone , dihydrofuran, tetrahydrofuran, dihydropyran, tetrahydropyran, dihydrothiophene, tetrahydrothiophene, dihydrothiopyran, tetrahydrothiopyran, dihydrogen Oxazole, tetrahydrogen Azole Oxazolidine) Azole, tetrahydroiso Azole Zolidine, dihydrothiazole, tetrahydrothiazole (thiazolidine), dihydroisothiazole, tetrahydroisothiazole (isothiazolidine), dihydrofurazan, tetrahydrofurazan, dihydrogen Diazole, tetrahydrogen Diazole Diazolidine), dihydrogen Tetrahydrogen Dihydrogen two Tetrahydrogen two , dihydrothiadiazole, tetrahydrothiadiazole (thiadiazolidine), dihydrothiazide Tetrahydrothiazide Dihydrothiazide Tetrahydrothiazide Morpholine, thiomorpholine, ring Butane and Thioxane ring and the like.

本發明中，「鹵素原子」為氟原子、氯原子、溴原子及碘原子。 In the present invention, the "halogen atom" is a fluorine atom, a chlorine atom, a bromine atom and an iodine atom.

本發明中，環Cy1表示之「5至6員單環式芳族雜環」為例如呋喃、噻吩、吡咯、異唑、唑、異噻唑、噻唑、吡唑、咪唑、1，2，3-三唑、1，2，4-三唑、四唑、吡啶、嗒、嘧啶、吡、1，2，4-三及1，2，3-三環等。 In the present invention, the "C to 6-membered monocyclic aromatic heterocyclic ring" represented by the ring Cy 1 is, for example, furan, thiophene, pyrrole, or different. Azole, Oxazole, isothiazole, thiazole, pyrazole, imidazole, 1,2,3-triazole, 1,2,4-triazole, tetrazole, pyridine, hydrazine Pyrimidine, pyridyl 1,2,4-three And 1,2,3-three Ring and so on.

本發明中，「可經取代」表示無取代或經任意數之取代基取代。任意之取代基數較好為1至10個，更好為1至8個，最好為1至6個。 In the present invention, "substitutable" means unsubstituted or substituted with any number of substituents. The number of the substituents is preferably from 1 to 10, more preferably from 1 to 8, most preferably from 1 to 6.

本發明中，環Cy1較好為苯、萘、環己烷、哌啶及5至10員單環式芳族雜環或二環式芳族雜環，更好為苯、環己烷、哌啶及5至6員單環式芳族雜環，又，更好為苯及5至6員單環 式芳族雜環，再更好為苯、呋喃、噻吩、吡咯、異唑、唑、異噻唑、噻唑、吡唑、咪唑、吡啶、嗒、嘧啶或吡，特好為苯、吡啶或吡唑，最好為苯或吡啶。 In the present invention, the ring Cy 1 is preferably benzene, naphthalene, cyclohexane, piperidine and a 5 to 10 membered monocyclic aromatic heterocyclic ring or a bicyclic aromatic heterocyclic ring, more preferably benzene or cyclohexane. Piperidine and 5 to 6 membered monocyclic aromatic heterocyclic ring, further preferably benzene and 5 to 6 membered monocyclic aromatic heterocyclic ring, more preferably benzene, furan, thiophene, pyrrole, or different Azole, Oxazole, isothiazole, thiazole, pyrazole, imidazole, pyridine, hydrazine Pyrimidine or pyridyl Particularly preferred is benzene, pyridine or pyrazole, preferably benzene or pyridine.

本發明中，R1較好為(1)鹵素原子、(2)C1-4烷基、(3)經鹵素原子取代之C1-4烷基、(4)環丙基、(5)環丁基、(6)經鹵素原子取代之環丙基、(7)經鹵素原子取代之環丁基、(8)氧雜環丁烷基或(9)經甲基取代之氧雜環丁烷基，更好為鹵素原子、甲基、三氟甲基、第三丁基、1，1-二氟乙基、異丙基、環丙基、氧雜環丁烷基或二氟甲基，再更好為鹵素原子、甲基或三氟甲基，最好為三氟甲基。 In the present invention, R 1 is preferably (1) a halogen atom, (2) a C1-4 alkyl group, (3) a C1-4 alkyl group substituted by a halogen atom, (4) a cyclopropyl group, and (5) a cyclobutene. a group, (6) a cyclopropyl group substituted with a halogen atom, (7) a cyclobutyl group substituted with a halogen atom, (8) an oxetanyl group or (9) a oxetane group substituted with a methyl group More preferably a halogen atom, a methyl group, a trifluoromethyl group, a tert-butyl group, a 1,1-difluoroethyl group, an isopropyl group, a cyclopropyl group, an oxetanyl group or a difluoromethyl group, More preferably, it is a halogen atom, a methyl group or a trifluoromethyl group, and is preferably a trifluoromethyl group.

本發明中，R2較好為異丙基、第二丁基、第三丁基、異丁基、氫原子、羥基、羧基、1-羥基-1-甲基乙基、2-羥基丙基、3-羥基-3-甲基-1-丁炔基、甲基磺醯基(-SO2CH3)、甲基磺醯胺(-SO2NHCH3)、二甲基磺醯胺(-SO2N(CH3)2)基或 In the present invention, R 2 is preferably isopropyl, t-butyl, tert-butyl, isobutyl, hydrogen, hydroxy, carboxy, 1-hydroxy-1-methylethyl, 2-hydroxypropyl. , 3-hydroxy-3-methyl-1-butynyl, methylsulfonyl (-SO 2 CH 3 ), methylsulfonamide (-SO 2 NHCH 3 ), dimethylsulfonamide (- SO 2 N(CH 3 ) 2 ) group or

(式中，Xa表示鍵結或氧原子，其他符號與上述[1]記載之符號同意義。)，更好為異丙基、甲基磺醯基、甲基磺醯胺、二甲基磺醯胺基或 (wherein, Xa represents a bond or an oxygen atom, and other symbols have the same meaning as the symbols described in the above [1].), more preferably isopropyl, methylsulfonyl, methylsulfonamide or dimethylsulfonate. Amidoxime or

(式中，Xa表示鍵結或氧原子，其他符號與上述[1]記載之符號同意義。)，又再更好為 (wherein, Xa represents a bond or an oxygen atom, and other symbols have the same meaning as the symbols described in the above [1].)

(式中，Xa表示鍵結或氧原子，其他符號與上述[1]記載之符號同意義。)。 (wherein, Xa represents a bond or an oxygen atom, and other symbols have the same meaning as the symbols described in the above [1].).

本發明中，X較好為鍵結或氧原子，更好為鍵結。 In the present invention, X is preferably a bond or an oxygen atom, more preferably a bond.

本發明中，Xa較好為鍵結。 In the present invention, Xa is preferably a bond.

本發明中，環Cy2較好為C3至10單環式碳環或5至10員單環式雜環或二環式雜環，更好為環丙烷、苯、環己烷、茚烷、四氫萘、吡喃、呋喃、噻吩、吡咯、異唑、唑、異噻唑、噻唑、吡唑、咪唑、三唑、吡啶、吡啶酮、嗒、嘧啶、吡、四氫吡喃、四氫噻喃、哌啶、嗎啉、硫代嗎啉、四氫吡啶、苯并二烷、哌、全氫茚、二氫苯并呋喃、二氫苯并噻吩、吲哚啉、苯并二茂、苯并硫醇、二氫苯并唑、二氫苯并噻唑、色滿、硫代色滿、四氫喹啉、二氫苯并二英、二氫苯并氧硫雜環己二烯、二氫苯并、吲哚、苯并呋喃、苯并噻吩、吲唑或四氫萘，最好為苯、環己烷、吡唑、咪唑、三唑或吡啶，特，好 為苯、吡啶、吡唑、咪唑或三唑，最好為苯或吡啶。 In the present invention, the ring Cy 2 is preferably a C3 to 10 monocyclic carbocyclic ring or a 5 to 10 membered monocyclic heterocyclic ring or a bicyclic heterocyclic ring, more preferably cyclopropane, benzene, cyclohexane or decane. Tetrahydronaphthalene, pyran, furan, thiophene, pyrrole, iso Azole, Oxazole, isothiazole, thiazole, pyrazole, imidazole, triazole, pyridine, pyridone, anthracene Pyrimidine, pyridyl , tetrahydropyran, tetrahydrothiopyran, piperidine, morpholine, thiomorpholine, tetrahydropyridine, benzodiazepine Alkane , all hydroquinone, dihydrobenzofuran, dihydrobenzothiophene, porphyrin, benzodiazepine Mao, benzo Mercaptan, dihydrobenzo Azole, dihydrobenzothiazole, chroman, thiochroman, tetrahydroquinoline, dihydrobenzo English, dihydrobenzothiazepine, dihydrobenzo , hydrazine, benzofuran, benzothiophene, oxazole or tetrahydronaphthalene, preferably benzene, cyclohexane, pyrazole, imidazole, triazole or pyridine, especially benzene, pyridine, pyrazole, imidazole Or a triazole, preferably benzene or pyridine.

本發明中，R6較好為鹵素原子、羥基、C1至4烷基、經鹵素原子取代之C1至4烷基、經羥基取代之C1至4烷基、C3至6環烷基、C1至4烷氧基、羧基、-CO2(C1至4烷基)、乙醯基醯胺基(-NHCOCH3)、膦醯基氧基及或磺醯胺基，更好為氟原子、氯原子、甲基、三氟甲基、乙基、正丙基、異丙基、環丙基、環丁基、環戊基、環己基、甲氧基、乙氧基、正丙氧基、異丙氧基、正丁氧基、第二丁氧基、第三丁氧基、異丁氧基、1-羥基丙基、1-羥基乙基、羥基甲基、羧基、甲氧基羰基、乙氧基羰基、乙醯基醯胺基、膦醯基氧基或磺醯胺基，最好為氟原子、氯原子、甲基、三氟甲基、乙基、正丙基、異丙基、甲氧基、乙氧基、正丙氧基、正丁氧基、羥基甲基、甲氧基羰基、乙醯基醯胺基、膦醯基氧基或磺醯胺基，特，好為氟原子、氯原子、甲基、三氟甲基、乙基、甲氧基或羥基甲基，最好為氟原子、氯原子、甲基或三氟甲基。 In the present invention, R 6 is preferably a halogen atom, a hydroxyl group, a C1 to 4 alkyl group, a C1 to 4 alkyl group substituted by a halogen atom, a C1 to 4 alkyl group substituted by a hydroxyl group, a C3 to 6 cycloalkyl group, and C1 to 4 alkoxy group, carboxyl group, -CO 2 (C1 to 4 alkyl group), ethoxylated fluorenylamino group (-NHCOCH 3 ), phosphinyloxy group and or sulfonylamino group, more preferably fluorine atom or chlorine atom , methyl, trifluoromethyl, ethyl, n-propyl, isopropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, methoxy, ethoxy, n-propoxy, isopropyl Oxyl, n-butoxy, second butoxy, tert-butoxy, isobutoxy, 1-hydroxypropyl, 1-hydroxyethyl, hydroxymethyl, carboxyl, methoxycarbonyl, ethoxy Alkylcarbonyl, acetamylamino, phosphinyloxy or sulfonylamino, preferably a fluorine atom, a chlorine atom, a methyl group, a trifluoromethyl group, an ethyl group, a n-propyl group, an isopropyl group, a Oxyl, ethoxy, n-propoxy, n-butoxy, hydroxymethyl, methoxycarbonyl, ethinylamino, phosphinyloxy or sulfonylamino, especially fluorine atom , chlorine atom, methyl, trifluoromethyl, ethyl, methoxy or hydroxy Group, preferably a fluorine atom, chlorine atom, methyl or trifluoromethyl.

本發明中，R3較好為氟原子、氯原子、甲基、三氟甲基或甲氧基，更好為氟原子。 In the present invention, R 3 is preferably a fluorine atom, a chlorine atom, a methyl group, a trifluoromethyl group or a methoxy group, more preferably a fluorine atom.

本發明中，R4較好為氫原子、氟原子、氯原子、甲基、三氟甲基或甲氧基，更好為氫原子、氟原子、氯原子或甲氧基，最好為氫原子或氟原子。 In the present invention, R 4 is preferably a hydrogen atom, a fluorine atom, a chlorine atom, a methyl group, a trifluoromethyl group or a methoxy group, more preferably a hydrogen atom, a fluorine atom, a chlorine atom or a methoxy group, preferably hydrogen. Atom or fluorine atom.

本發明中，Y較好為氧原子。 In the present invention, Y is preferably an oxygen atom.

本發明中，Z較好為 In the present invention, Z is preferably

更好為 Better for

(式中，所有符號與上述[1]記載之符號同意義)。 (In the formula, all symbols have the same meaning as the symbols described in [1] above).

本發明中，R5較好為羥基或羥基甲基。 In the present invention, R 5 is preferably a hydroxyl group or a hydroxymethyl group.

本發明中，R7較好為C1至6烷基，更好為乙基、正丙基、異丙基或第三丁基，又更好為正丙基。 In the present invention, R 7 is preferably a C1 to 6 alkyl group, more preferably an ethyl group, a n-propyl group, an isopropyl group or a t-butyl group, and more preferably a n-propyl group.

本發明中，p較好為0至2之整數。 In the present invention, p is preferably an integer of from 0 to 2.

本發明中，q較好為0至2之整數。 In the present invention, q is preferably an integer of 0 to 2.

本發明中，r較好為0至2之整數。 In the present invention, r is preferably an integer of from 0 to 2.

本發明中，w較好為2至4之整數。 In the present invention, w is preferably an integer of from 2 to 4.

本發明中，u較好為0至1之整數。 In the present invention, u is preferably an integer of from 0 to 1.

本發明中，pa較好為0至2之整數。 In the present invention, pa is preferably an integer of 0 to 2.

本發明中，pb較好為0至2之整數。 In the present invention, pb is preferably an integer of from 0 to 2.

本發明中，後述之pc較好為0至1整數。 In the present invention, pc described later is preferably an integer of 0 to 1.

本發明中，後述之ra較好為0至1之整數。 In the present invention, ra, which will be described later, is preferably an integer of from 0 to 1.

本發明中，後述之t較好為0至2之整數。 In the present invention, t to be described later is preferably an integer of 0 to 2.

本發明中，通式(I)較好為上述之環Cy1、R1、R2、X、環Cy2、R6、R3、R4、Y、Z、R5、R7、p、q、r、w、u、pa、pb、pc、 ra及t以各個較佳之定義組合，更好為以下所示化合物、其鹽、其N-氧化物、其溶劑化物或該等之前驅藥。 In the present invention, the general formula (I) is preferably the above-mentioned ring Cy 1 , R 1 , R 2 , X, ring Cy 2 , R 6 , R 3 , R 4 , Y, Z, R 5 , R 7 , p , q, r, w, u, pa, pb, pc, ra and t are combined in each preferred definition, more preferably a compound shown below, a salt thereof, an N-oxide thereof, a solvate thereof or such precursors medicine.

(式中，所有符號與上述[1]及[6]記載之符號同意義。) (In the formula, all symbols have the same meaning as the symbols described in [1] and [6] above.)

通式(I)表示之化合物中，通式(I-1-a)表示之化合物更好為下述通式(I-1-a-1)或通式(I-1-a-2)表示之化合物、其鹽、其N-氧化物、其溶劑化物或該等之前驅藥。 In the compound represented by the formula (I), the compound represented by the formula (I-1-a) is more preferably a formula (I-1-a-1) or a formula (I-1-a-2) A compound, a salt thereof, an N-oxide thereof, a solvate thereof, or such a prodrug.

(式中，ra表示0至3之整數，t表示0至4之整數，其他符號與上述[1]記載之符號同意義。)。 (wherein, ra represents an integer of 0 to 3, and t represents an integer of 0 to 4, and other symbols have the same meaning as the symbols described in the above [1].).

通式(I)表示之化合物中，通式(I-1-a-1)表示之化合物或通式(I-1-a-2)表示之化合物特好為下述通式(I-1-a-1-i)、通式(I-1-a-1-ii)、通式(I-1-a-1-iii)、通式(I-1-a-2-i)、通式(I-1-a-2-ii)或通式(I-1-a-2-iii)表示之化合物、其鹽、其N-氧化物、其溶劑化物或該等之前驅藥 In the compound represented by the formula (I), the compound represented by the formula (I-1-a-1) or the compound represented by the formula (I-1-a-2) is particularly preferably the following formula (I-1). -a-1-i), general formula (I-1-a-1-ii), general formula (I-1-a-1-iii), general formula (I-1-a-2-i), a compound represented by the formula (I-1-a-2-ii) or the formula (I-1-a-2-iii), a salt thereof, an N-oxide thereof, a solvate thereof or the like

(式中，ra表示0至3之整數，t表示0至4之整數，pc表示0至2之整數，其他符號與上述[1]及[6]記載之符號同意義。)。 (wherein, ra represents an integer of 0 to 3, t represents an integer of 0 to 4, pc represents an integer of 0 to 2, and other symbols have the same meaning as the symbols described in the above [1] and [6].).

通式(I)表示之化合物中，通式(I-1-a-1-i)表示之化合物、通式(I-1-a-1-ii)表示之化合物、通式(I-1-a-1-iii)表示之化合物、通式(I-1-a-2-i)表示之化合物、通式(I-1-a-2-ii)表示之化合物或通式(I-1-a-2-iii)表示之化合物較好為該等通式之環Cy2為C3至10單環式碳環或5至10員單環式雜環或二環式雜環，R1為(1)鹵素原子、(2)C1至4烷基、(3)經鹵素原子取代之C1至4烷基、(4)環丙基、(5)環丁基、(6)經鹵素原子取代之環丙基、(7)經鹵素原子取代之環丁基、(8)氧雜環丁烷基及(9)經甲基取代之氧雜環丁烷基，R3為氟原子、氯原子、甲基、三氟甲基及甲氧基，R4為氟原子、氯原子、甲基、三氟甲基及甲氧基，R5為羥基及羥基甲基，R6為(1)鹵素原子、(2)羥基、(3)C1至4烷基、(4)經鹵素原子取代之C1至4烷基、(5)經羥基取代之C1至4烷基、(6)C3至6環烷基、(7)C1至4烷氧基、(8)羧基、(9)-CO2(C1至4烷基)、(10)乙醯基醯胺基、(11)膦醯基氧基及(12)磺醯胺基，pa為0至2之整數，pb為0至2之整數，pc為0至1之整數，q為0至2之整數，ra為0至1之整數，t為0至2之整數，u為0至1之整數及w為2至4之整數表示之化合物、其鹽、其N-氧化物、其溶劑化物或該等之前驅藥，更好為該等通式之環Cy2為環丙烷、苯、環己烷、茚烷、四氫萘、吡喃、呋喃、噻吩、吡咯、異唑、唑、異噻唑、噻唑、吡唑、咪唑、三唑、吡啶、吡啶酮、嗒、嘧啶、吡、四氫吡喃、四氫噻喃、哌啶、嗎啉、硫代嗎啉、四氫吡啶、苯并二烷、哌、全氫茚、二氫苯并呋喃、二氫苯并噻吩、吲哚啉、苯并二茂、 苯并硫醇、二氫苯并唑、二氫苯并噻唑、色滿、硫代色滿、四氫喹啉、二氫苯并二英、二氫苯并氧硫雜環己二烯、二氫苯并、吲哚、苯并呋喃、苯并噻吩、吲唑及四氫萘，R1為(1)鹵素原子、(2)C1至4烷基、(3)經鹵素原子取代之C1至4烷基、(4)環丙基、(5)環丁基、(6)經鹵素原子取代之環丙基、(7)經鹵素原子取代之環丁基、(8)氧雜環丁烷基及(9)經甲基取代之氧雜環丁烷基，R3為氟原子、氯原子、甲基、三氟甲基及甲氧基，R4為氟原子、氯原子、甲基、三氟甲基及甲氧基，R5為羥基及羥基甲基，R6為(1)鹵素原子、(2)羥基、(3)C1至4烷基、(4)經鹵素原子取代之C1至4烷基、(5)經羥基取代之C1至4烷基、(6)C3至6環烷基、(7)C1至4烷氧基、(8)羧基、(9)-CO2(C1至4烷基)、(10)乙醯基醯胺基、(11)膦醯基氧基及(12)磺醯胺基，pa為0至2之整數，pb為0至2之整數，pc為0至1之整數，q為0至2之整數，ra為0至1之整數，t為0至2之整數，u為0至1之整數及w為2至4之整數表示之化合物、其鹽、其N-氧化物、其溶劑化物或該等之前驅藥，又更好為該等通式之環Cy2為苯、吡啶、吡唑、咪唑及三唑，R1為(1)鹵素原子、(2)C1至4烷基、(3)經鹵素原子取代之C1至4烷基、(4)環丙基、(5)環丁基、(6)經鹵素原子取代之環丙基、(7)經鹵素原子取代之環丁基、(8)氧雜環丁烷基及(9)經甲基取代之氧雜環丁烷基，R3為氟原子、氯原子、甲基、三氟甲基及甲氧基，R4為氟原子、氯原子、甲基、三氟甲基及甲氧基，R5為羥基及羥基甲基，R6為(1)鹵素原子、(2)羥基、(3)C1至4烷基、(4)經鹵素原子取代之C1至4烷基、(5)經羥基取代之C1至4烷基、(6)C3至6環烷基、(7)C1至4烷氧基、(8)羧基、(9)-CO2(C1至4 烷基)、(10)乙醯基醯胺基、(11)膦醯基氧基及(12)磺醯胺基，pa為0至2之整數，pb為0至2之整數，pc為0至1之整數，q為0至2之整數，ra為0至1之整數，t為0至2之整數，u為0至1之整數及w為2至4之整數表示之化合物、其鹽、其N-氧化物、其溶劑化物或該等之前驅藥。 In the compound represented by the formula (I), the compound represented by the formula (I-1-a-1-i), the compound represented by the formula (I-1-a-1-ii), and the formula (I-1) -a-1-iii) a compound represented by the formula, a compound represented by the formula (I-1-a-2-i), a compound represented by the formula (I-1-a-2-ii) or a formula (I- The compound represented by 1-a-2-iii) is preferably a ring of the formula: Cy 2 is a C3 to 10 monocyclic carbocyclic ring or a 5 to 10 membered monocyclic heterocyclic ring or a bicyclic heterocyclic ring, R 1 Is (1) a halogen atom, (2) a C1 to 4 alkyl group, (3) a C1 to 4 alkyl group substituted by a halogen atom, (4) a cyclopropyl group, (5) a cyclobutyl group, (6) a halogen atom Substituted cyclopropyl, (7) cyclobutyl substituted by halogen atom, (8) oxetanyl group and (9) methyl substituted oxetanyl group, R 3 is a fluorine atom, chlorine Atom, methyl, trifluoromethyl and methoxy, R 4 is a fluorine atom, a chlorine atom, a methyl group, a trifluoromethyl group and a methoxy group, R 5 is a hydroxyl group and a hydroxymethyl group, and R 6 is (1) a halogen atom, (2) a hydroxyl group, (3) a C1 to 4 alkyl group, (4) a C1 to 4 alkyl group substituted by a halogen atom, (5) a C1 to 4 alkyl group substituted by a hydroxyl group, (6) C3 to 6 Cycloalkyl, (7) C1 to 4 alkoxy, (8) carboxyl, (9)-CO 2 (C1 to 4 alkyl), (10) Ethyl mercaptoamine, (11) phosphinyloxy and (12) sulfonylamino, pa is an integer from 0 to 2, pb is an integer from 0 to 2, and pc is an integer from 0 to 1. q is an integer from 0 to 2, ra is an integer from 0 to 1, t is an integer from 0 to 2, u is an integer from 0 to 1, and w is an integer represented by an integer from 2 to 4, a salt thereof, and N- thereof Oxides, solvates thereof or such prodrugs, more preferably the ring Cy 2 of the formula is cyclopropane, benzene, cyclohexane, decane, tetrahydronaphthalene, pyran, furan, thiophene, pyrrole, different Azole, Oxazole, isothiazole, thiazole, pyrazole, imidazole, triazole, pyridine, pyridone, anthracene Pyrimidine, pyridyl , tetrahydropyran, tetrahydrothiopyran, piperidine, morpholine, thiomorpholine, tetrahydropyridine, benzodiazepine Alkane , all hydroquinone, dihydrobenzofuran, dihydrobenzothiophene, porphyrin, benzodiazepine Mao, benzo Mercaptan, dihydrobenzo Azole, dihydrobenzothiazole, chroman, thiochroman, tetrahydroquinoline, dihydrobenzo English, dihydrobenzothiazepine, dihydrobenzo , hydrazine, benzofuran, benzothiophene, oxazole and tetrahydronaphthalene, R 1 is (1) a halogen atom, (2) a C1 to 4 alkyl group, and (3) a C1 to 4 alkyl group substituted by a halogen atom. (4) cyclopropyl, (5) cyclobutyl, (6) a cyclopropyl group substituted with a halogen atom, (7) a cyclobutyl group substituted with a halogen atom, (8) oxetanyl group and 9) a methyl-substituted oxetanyl group, R 3 is a fluorine atom, a chlorine atom, a methyl group, a trifluoromethyl group and a methoxy group, and R 4 is a fluorine atom, a chlorine atom, a methyl group, a trifluoromethyl group. And methoxy, R 5 is hydroxy and hydroxymethyl, and R 6 is (1) halogen atom, (2) hydroxy group, (3) C1 to 4 alkyl group, (4) C1 to 4 alkyl group substituted by halogen atom a group, (5) a C1 to 4 alkyl group substituted by a hydroxyl group, (6) a C3 to 6 cycloalkyl group, (7) a C1 to a 4 alkoxy group, a (8) carboxyl group, and (9)-CO 2 (C1 to 4) Alkyl), (10) ethyl hydrazide amide, (11) phosphinyloxy and (12) sulfonylamino, pa is an integer from 0 to 2, pb is an integer from 0 to 2, pc is 0 An integer up to 1, q is an integer from 0 to 2, ra is an integer from 0 to 1, t is an integer from 0 to 2, u is an integer from 0 to 1, and w is an integer represented by an integer from 2 to 4, and a salt thereof , its N-oxide, its solvate or The prodrug, and better for such a ring of formula Cy 2 is benzene, pyridine, pyrazole, imidazole, and triazole, R 1 is (1) a halogen atom, (2) C1 to C4 alkyl, (3) a C1 to 4 alkyl group substituted by a halogen atom, (4) a cyclopropyl group, a (5) cyclobutyl group, (6) a cyclopropyl group substituted with a halogen atom, (7) a cyclobutyl group substituted by a halogen atom, 8) oxetanyl group and (9) methyl substituted oxetanyl group, R 3 is a fluorine atom, a chlorine atom, a methyl group, a trifluoromethyl group and a methoxy group, and R 4 is a fluorine atom. , chlorine atom, methyl group, trifluoromethyl group and methoxy group, R 5 is a hydroxyl group and a hydroxymethyl group, and R 6 is (1) a halogen atom, (2) a hydroxyl group, (3) a C1 to a 4 alkyl group, (4) a C1 to 4 alkyl group substituted with a halogen atom, (5) a C1 to 4 alkyl group substituted by a hydroxyl group, (6) a C3 to 6 cycloalkyl group, (7) a C1 to 4 alkoxy group, a (8) carboxyl group, (9) -CO 2 (C1 to 4 alkyl), (10) ethyl hydrazide amide, (11) phosphinyloxy and (12) sulfonylamino, pa is an integer from 0 to 2, pb An integer from 0 to 2, pc is an integer from 0 to 1, q is an integer from 0 to 2, ra is an integer from 0 to 1, t is an integer from 0 to 2, u is an integer from 0 to 1 and w is 2. a compound represented by an integer of 4, a salt thereof, and an N- Thereof, or solvates of such prodrugs.

通式(I)表示之化合物中，通式(I-1-a-1)表示之化合物或通式(I-1-a-2)表示之化合物最好為(1)1-[5，6’-雙(三氟甲基)-2，3’-二吡啶-3-基]-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(2)1-[5，6’-雙(三氟甲基)-2，3’-二吡啶-3-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(3)1-[2-(3，4-二甲基苯基)-5-(三氟甲基)-3-吡啶基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(4)1-[2-(3，4-二甲基苯基)-5-(三氟甲基)-3-吡啶基]-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(5)1-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-苯基-5-(三氟甲基)-3-吡啶基]脲、(6)1-[2-(2-甲基苯基)-5-(三氟甲基)-3-吡啶基]-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(7)1-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-苯基-5-(三氟甲基)-3-吡啶基]脲、(8)1-[2-(2-甲基苯基)-5-(三氟甲基)-3-吡啶基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(9)1-[2-(4-甲基苯基)-5-(三氟甲基)-3-吡啶基]-3-(2-{4-[2-(2-側氧基 -1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(10)1-[2-(3-甲基苯基)-5-(三氟甲基)-3-吡啶基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(11)1-[2-(3，4-二甲基苯基)-5-(三氟甲基)-3-吡啶基]-3-(2-{4-[2-(2-側氧基-1-氮呯基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(12)1-[2-(1-甲基-1H-吡唑-4-基)-5-(三氟甲基)-3-吡啶基]-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(13)1-[1-(3，4-二甲基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(14)1-[1-(3，4-二甲基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(15)1-[1-(2，3-二氫-1H-茚-5-基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(16)1-[1-(2，3-二氫-1H-茚-5-基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{2-氟-4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(17)1-[1-(2，3-二氫-1H-茚-5-基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(18)1-[1-(2，3-二氫-1H-茚-5-基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{3-氟-4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、 (19)1-(2-{2-氯-4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[1-(2，3-二氫-1H-茚-5-基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]脲、(20)1-[1-(2，3-二氫-1H-茚-5-基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-氮呯基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(21)1-{1-[3-(羥基甲基)-4-甲基苯基]-3-(2-甲基-2-丙基)-1H-吡唑-5-基}-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(22)1-{1-[4-(羥基甲基)-3-甲基苯基]-3-(2-甲基-2-丙基)-1H-吡唑-5-基}-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(23)1-{3-(2-甲基-2-丙基)-1-[4-甲基-3-(三氟甲基)苯基]-1H-吡唑-5-基}-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(24)1-[3-(2-甲基-2-丙基)-1-[3，4，5-三甲基苯基]-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(25)1-[3-(2-甲基-2-丙基)-1-[3，4，5-三甲基苯基]-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(26)1-[1-(4-氟苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(27)1-[1-(4-甲氧基-3，5-二甲基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5- 基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(28)1-{3-(2-甲基-2-丙基)-1-[4-(三氟甲基)苯基]-1H-吡唑-5-基}-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(29)1-[3-(2-甲基-2-丙基)-1-苯基-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(30)1-[1-(4-甲基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(31)1-[1-均三甲苯基-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(32)1-[1-(2-甲基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(33)1-[1-(2，3-二氫-1-苯并呋喃-5-基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(34)1-[1-(2，3-二甲基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(35)1-[1-(4-甲氧基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(36)1-[1-(4-氟-2-甲基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基) 脲、(37)1-[1-(2-氟苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(38)1-[1-(2-氟-3-甲基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(39)1-[1-(3-氟苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(40)1-[1-(2-甲基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(41)甲基3-[3-(2-甲基-2-丙基)-5-{[(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)胺基甲醯基]胺基}-1H-吡唑-1-基]苯甲酸酯、(42)N-{4-[3-(2-甲基-2-丙基)-5-{[(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)胺基甲醯基]胺基}-1H-吡唑-1-基]苯基}乙醯胺、(43)1-[1-(1，3-苯并二茂-5-基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(44)1-[3-(2-甲基-2-丙基)-1-苯基-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(45)1-[1-(2，3-二甲氧基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、 (46)1-[1-(2-氟-4-甲氧基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(47)1-{1-[2-氟-4-(三氟甲基)苯基]-3-(2-甲基-2-丙基)-1H-吡唑-5-基}-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(48)1-[1-(2-氯-4-甲基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(49)1-[1-(2，5-二甲基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(50)1-[1-(2-氟苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(51)1-[1-(2-氟-4-甲基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(52)1-[1-(4-氟苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(53)1-[1-(3-丁氧基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(54)1-[3-(2-甲基-2-丙基)-1-(4-丙基苯基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(55)1-[1-(3-氯-4-甲基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(56)1-{3-(2-甲基-2-丙基)-1-[4-(三氟甲基)苯基]-1H-吡唑-5-基}-3- (2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(57)1-[1-(4-甲基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(58)1-[1-(3-甲氧基-4-甲基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(59)1-[1-(3-甲基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(60)1-[1-(3，4-二氫-2H-色烯-6-基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(61)1-{1-[4-(3-羥基丙基)苯基]-3-(2-甲基-2-丙基)-1H-吡唑-5-基}-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(62)1-[1-(3-甲氧基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(63)1-[1-(2，3-二氫-1，4-苯并二英-6-基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(64)1-[1-(2，5-二甲基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(65)1-{1-[3-(2-羥基乙基)苯基]-3-(2-甲基-2-丙基)-1H-吡唑-5- 基}-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(66)1-[1-(3，5-二甲基-4-丙氧基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(67)1-[1-(3-異丙基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(68)1-[1-(2，3-二氫-1-苯并呋喃-5-基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(69)1-[1-(2-氯-6-甲基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(70)1-[1-(3-氟-2-甲基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(71)1-[1-(5-氟-2-甲基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(72)1-[1-(2-乙基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(73)1-[1-(2-甲基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-氮呯基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(74)1-[1-(2-氯苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2- 側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(75)1-{3-(2-甲基-2-丙基)-1-[3-(三氟甲基)苯基]-1H-吡唑-5-基}-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(76)1-[1-(3-乙基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(77)1-[1-(2-氯-4-氟苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(78)1-[1-(4-氯-2-甲基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(79)1-[1-(3-甲氧基-2，4-二甲基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(80)1-[1-(2-甲氧基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(81)1-[1-(2-氟-5-甲基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(82)1-[1-(2-氯-5-甲基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(83)1-[1-(2-氟-4-甲基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基) 脲、(84)1-[1-(3-氟-2，4-二甲基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(85)1-[1-(2-氯-4-甲基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(86)4-[3-(2-甲基-2-丙基)-5-{[(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)胺基甲醯基]胺基}-1H-吡唑-1-基]苯磺醯胺、(87)1-[1-(2-甲基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(6-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)脲、(88)1-(5-甲基-6-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)-3-[1-(2-甲基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]脲、(89)1-[1-(1-甲基-1H-吲哚-5-基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(90)1-[1-(1-甲基-1H-吲唑-5-基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(91)1-[1-(2-甲基苯基)-3-(三氟甲基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(92)1-[1-(3，4-二甲基苯基)-3-(三氟甲基)-1H-吡唑-5-基]-3-(2-{4-[2- (2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(93)1-[3-(1，1-二氟乙基)-1-(2-甲基苯基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(94)1-[1-(4-氟苯基)-3-(三氟甲基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(95)1-[1-(2-甲基苯基)-3-(三氟甲基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(96)1-[3-(1，1-二氟乙基)-1-(2-甲基苯基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(97)1-(3-環丙基-1-苯基-1H-吡唑-5-基)-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(98)1-(3-異丙基-1-苯基-1H-吡唑-5-基)-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(99)1-[1-(6-甲氧基-3-吡啶基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(100)1-[3-(2-甲基-2-丙基)-1-(6-甲基-3-吡啶基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(101)1-[3-(2-甲基-2-丙基)-1-(3-吡啶基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(102)1-[1-(6-異丙氧基-3-吡啶基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、 (103)1-[3-(2-甲基-2-丙基)-1-(6-甲基-3-吡啶基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(104)1-[3-(2-甲基-2-丙基)-1-(3-吡啶基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(105)1-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-(4-吡啶基)-5-(三氟甲基)苯基]脲、(106)1-[2-(4-嗎啉基)-5-(三氟甲基)苯基]-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(107)1-[2-(4-甲基-1-哌基)-5-(三氟甲基)苯基]-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(108)1-[3-(2-甲基-2-丙基)-1-(1，2，3，4-四氫-2-萘基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(109)1-[3-(2-甲基-2-丙基)-1-(四氫-2H-吡喃-4-基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(110)1-[1-環己基-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(111)1-[2-環己基-5-(三氟甲基)-3-吡啶基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(112)1-[2-(3，4-二甲基苯基)-5-甲基-3-吡啶基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(113)1-[2-(3，4-二甲基苯基)-3-吡啶基]-3-(2-{4-[2-(2-側氧基-1-吡咯 啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(114)1-(3-異丙基-1-苯基-1H-吡唑-5-基)-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(115)1-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-(3-吡啶基)-5-(三氟甲基)苯基]脲、(116)1-(6-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)-3-[2-(4-吡啶基)-5-(三氟甲基)苯基]脲、(117)1-[6’-甲基-5-(三氟甲基)-2，3’-二吡啶-3-基]-3-(6-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)脲、(118)1-(6-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)-3-[2-(3-吡啶基)-5-(三氟甲基)苯基]脲、(119)1-(6-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)-3-[2-苯基-5-(三氟甲基)-3-吡啶基]脲、(120)1-(6-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)-3-[5-(三氟甲基)-2，4’-二吡啶-3-基]脲、(121)1-[2-(4-甲基苯基)-5-(三氟甲基)-3-吡啶基]-3-(6-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)脲、(122)1-[2-(6-甲基-3-吡啶基)-5-(三氟甲基)苯基]-3-(6-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)脲、(123)1-[1-氧負離子基(oxido)-2-苯基-5-(三氟甲基)-3-吡啶基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(124)1-(6-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)-3-{5-(三氟甲基)-2-[6-(三氟甲基)-3-吡啶基]苯基}脲、 (125)1-[2-(6-甲基-3-吡啶基)-5-(三氟甲基)苯基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(126)1-(6-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)-3-[5-(三氟甲基)-2，3’-二吡啶-3-基]脲、(127)1-[2-(6-甲氧基-3-吡啶基)-5-(三氟甲基)苯基]-3-(6-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)脲、(128)1-[2-(3-羥基苯基)-5-(三氟甲基)-3-吡啶基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(129)1-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[5-(三氟甲基)-2，3’-二吡啶-3-基]脲、(130)1-[2-(1-氧負離子基-4-吡啶基)-5-(三氟甲基)苯基]-3-(6-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)脲、(131)1-(6-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)-3-[4-(三氟甲基)-2-聯苯基]脲、(132)1-[2-(4-羥基苯基)-5-(三氟甲基)-3-吡啶基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(133)1-[2-(1-氧負離子基-4-吡啶基)-5-(三氟甲基)苯基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(134)1-[2-(1-氧負離子基-3-吡啶基)-5-(三氟甲基)苯基]-3-(6-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)脲、(135)1-[2-(1-氧負離子基-3-吡啶基)-5-(三氟甲基)苯基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(136)1-[2-(2-甲氧基苯基)-5-(三氟甲基)-3-吡啶基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、 (137)1-[2-(3-甲氧基苯基)-5-(三氟甲基)-3-吡啶基}3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(138)1-[2-(2-羥基苯基)-5-(三氟甲基)-3-吡啶基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(139)1-(1-氧負離子基-6-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)-3-[2-苯基-5-(三氟甲基)-3-吡啶基]脲、(140)1-[2-(4-甲氧基苯基)-5-(三氟甲基)-3-吡啶基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(141)1-[2-環己基-5-(三氟甲基)-3-吡啶基]-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(142)1-[3-(2-甲基-2-丙基)-1-苯基-1H-吡唑-5-基]-3-(6-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)脲、(143)1-(6-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)-3-[2-苯基-5-(三氟甲基)-3-吡啶基]脲、(144)1-(6-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)-3-[2-(4-吡啶基)-5-(三氟甲基)苯基]脲、(145)1-(6-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)-3-[2-(3-吡啶基)-5-(三氟甲基)苯基]脲、(146)1-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[5-(三氟甲基)-2，4’-二吡啶-3-基]脲、(147)1-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-(3-吡啶基)-5-(三氟甲基)苯基]脲、(148)1-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[5-(三氟甲基)-2，3’-二吡啶-3-基]脲、 (149)1-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-(4-吡啶基)-5-(三氟甲基)苯基]脲、(150)1-[2-(6-甲基-3-吡啶基)-5-(三氟甲基)苯基]-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(151)磷酸二氫3-[3-{[(2{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-嘧啶基]胺基甲醯基}胺基)-5-(三氟甲基)-2-吡啶基]苯基、(152)1-[6-({6-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]-3-吡啶基}氧基)-3-吡啶基]-3-[2-苯基-5-(三氟甲基)-3-吡啶基]脲、(153)1-[2-(4-{2-[(4S)-4-羥基-2-側氧基-1-吡咯啶基]-1，3-噻唑-5-基}苯氧基)-5-嘧啶基]-3-[2-苯基-5-(三氟甲基)-3-吡啶基]脲、(154)1-(2-{2-氟-4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-苯基-5-(三氟甲基)-3-吡啶基]脲、(155)1-(2-{2-氟-4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-(3-吡啶基)-5-(三氟甲基)苯基]脲、(156)1-[2-(1-氧負離子基-3-吡啶基)-5-(三氟甲基)-3-吡啶基]-3-(6-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)脲、(157)1-[2-(1-氧負離子基-3-吡啶基)-5-(三氟甲基)-3-吡啶基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(158)1-(6-{2-氟-4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)-3-[2-苯基-5-(三氟甲基)-3-吡啶基]脲、(159)1-(6-{2-氟-4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)-3-[2-(3-吡啶基)-5-(三氟甲基)苯基]脲、 (160)1-[2-(2-甲基-4-吡啶基)-5-(三氟甲基)苯基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(161)1-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-(4-哌啶基)-5-(三氟甲基)苯基]脲、(162)1-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-(1，2，3，6-四氫-4-吡啶基)-5-(三氟甲基)苯基]脲、(163)1-(4-甲基-6-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)-3-[2-苯基-5-(三氟甲基)-3-吡啶基]脲、(164)1-(4-甲基-6-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)-3-[2-(3-吡啶基)-5-(三氟甲基)苯基]脲、(165)1-[2-(1-甲基-4-哌啶基)-5-(三氟甲基)苯基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(166)1-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-(1H-吡唑-3-基)-5-(三氟甲基)苯基]脲、(167)1-(2-甲基-6-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)-3-[2-(3-吡啶基)-5-(三氟甲基)苯基]脲、(168)1-(2-甲基-6-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)-3-[2-苯基-5-(三氟甲基)-3-吡啶基]脲、(169)1-[2-(1H-咪唑-1-基)-5-(三氟甲基)苯基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(170)1-(2-{4-[2-(2-甲基-5-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-苯基-5-(三氟甲基)-3-吡啶基]脲、(171)1-(2-{4-[2-(2-甲基-5-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-(3-吡啶基)-5-(三氟甲基)苯基]脲、 (172)1-[5-(2-甲基-2-丙基)-2-(3-吡啶基)苯基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(173)1-(5-甲基-6-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)-3-[2-苯基-5-(三氟甲基)-3-吡啶基]脲、(174)1-(5-甲基-6-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)-3-[2-(3-吡啶基)-5-(三氟甲基)苯基]脲、(175)1-[2-(1-甲基-6-側氧基-1，6-二氫-3-吡啶基)-5-(三氟甲基)苯基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(176)1-[2-(6-側氧基-1，6-二氫-3-吡啶基)-5-(三氟甲基)苯基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(177)1-[5-(3-氧雜環丁烷基)-2-苯基-3-吡啶基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(178)1-(2-{4-[2-(2-側氧基-1-氮雜環丁烷基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-(3-吡啶基)-5-(三氟甲基)苯基]脲、(179)1-[5-(3-氧雜環丁烷基)-2-(3-吡啶基)苯基-]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(180)1-(2-{3-甲基-4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-(3-吡啶基)-5-(三氟甲基)苯基]脲、(181)1-[2-(4-{2-[4-(羥基甲基)-2-側氧基-1-吡咯啶基]-1，3-噻唑-5-基}苯氧基)-5-嘧啶基]-3-[2-(3-吡啶基)-5-(三氟甲基)苯基]脲、(182)1-[2-({6-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]-3-吡啶基}氧基)-5-嘧啶基]-3-[2-(3-吡啶基)-5-(三氟甲基)苯基]脲、 (183)1-[2-(3-氧雜環丁烷基)-5-(三氟甲基)苯基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(184)1-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-(1H-吡唑-1-基)-5-(三氟甲基)苯基]脲、(185)1-[5-氟-2-(1H-咪唑-1-基)苯基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(186)1-[2-(4-甲基-1H-咪唑-1-基)-5-(三氟甲基)苯基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(187)1-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-(1H-1，2，3-三唑-1-基)-5-(三氟甲基)苯基]脲、(188)1-[2-(4-{2-[3-(2-羥基-2-丙基)-2-側氧基-1-吡咯啶基]-1，3-噻唑-5-基}苯氧基)-5-嘧啶基]-3-[2-(3-吡啶基)-5-(三氟甲基)苯基]脲、(189)1-[2-(2-甲基-1H-咪唑-1-基)-5-(三氟甲基)苯基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(190)1-[2-(1H-咪唑-1-基)-5-(三氟甲基)苯基]-3-[2-({6-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]-3-吡啶基}氧基)-5-嘧啶基]脲、(191)1-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-(4H-1，2，4-三唑-4-基)-5-(三氟甲基)苯基]脲、(192)1-[6’-甲基-5-(三氟甲基)-2，3’-二吡啶-3-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(193)1-[2-(4-{2-[3-(2-羥基-2-丙基)-2-側氧基-1-吡咯啶基]-1，3-噻唑-5-基}苯氧基)-5-嘧啶基]-3-[2-苯基-5-(三氟甲基)-3-吡啶基]脲、(194)1-[5-氟-2-(3-吡啶基)苯基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、 (195)1-(5-甲氧基-6-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)-3-[2-苯基-5-(三氟甲基)-3-吡啶基]脲、(196)1-[2-(2-甲基-3-吡啶基)-5-(三氟甲基)苯基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(197)1-[2-(4-甲基-3-吡啶基)-5-(三氟甲基)苯基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(198)1-(5-氟-2，3’-二吡啶-3-基)-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(199)1-[2-(5-甲基-3-吡啶基)-5-(三氟甲基)苯基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(200)1-[5-氟-2-(4-吡啶基)苯基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(201)1-[2-(1-甲基-1H-咪唑-4-基)-5-(三氟甲基)-3-吡啶基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(202)1-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[5-(三氟甲基)-2，2’-二吡啶-3-基]脲、(203)1-[5-氟-2-(2-吡啶基)苯基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、或(204)1-[2-環丙基-5-(三氟甲基)-3-吡啶基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、其鹽、其N-氧化物、其溶劑化物或該等之前驅藥。 In the compound represented by the formula (I), the compound represented by the formula (I-1-a-1) or the compound represented by the formula (I-1-a-2) is preferably (1) 1-[5, 6'-bis(trifluoromethyl)-2,3'-dipyridin-3-yl]-3-(2-{4-[2-(2-o-oxy-1-piperidyl)-1 , 3-thiazole-5-yl]phenoxy}-5-pyrimidinyl)urea, (2) 1-[5,6'-bis(trifluoromethyl)-2,3'-dipyridine-3- 3-(2-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (3) 1-[2-(3,4-Dimethylphenyl)-5-(trifluoromethyl)-3-pyridyl]-3-(2-{4-[2-(2- side) Oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (4) 1-[2-(3,4-dimethylphenyl) -5-(Trifluoromethyl)-3-pyridyl]-3-(2-{4-[2-(2-o-oxy-1-piperidyl)-1,3-thiazole-5- (5-phenoxy}-5-pyrimidinyl)urea, (5) 1-(2-{4-[2-(2-o-oxy-1-piperidyl)-1,3-thiazole-5- (phenoxy}-5-pyrimidinyl)-3-[2-phenyl-5-(trifluoromethyl)-3-pyridyl]urea, (6) 1-[2-(2-methyl Phenyl)-5-(trifluoromethyl)-3-pyridyl]-3-(2-{4-[2-(2-o-oxy-1-piperidyl)-1,3-thiazole- 5-yl]phenoxy}-5-pyrimidinyl)urea, (7) 1-(2-{4-[2-(2-o-oxy-1-pyrrolidine) )-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-[2-phenyl-5-(trifluoromethyl)-3-pyridyl]urea, (8) 1-[2-(2-methylphenyl)-5-(trifluoromethyl)-3-pyridyl]-3-(2-{4-[2-(2-o-oxy-1-pyrrole) Pyridyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (9) 1-[2-(4-methylphenyl)-5-(trifluoromethyl )-3-pyridyl]-3-(2-{4-[2-(2-o-oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5- Pyrimidinyl)urea, (10) 1-[2-(3-methylphenyl)-5-(trifluoromethyl)-3-pyridyl]-3-(2-{4-[2-(2) -Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (11) 1-[2-(3,4-dimethyl Phenyl)-5-(trifluoromethyl)-3-pyridyl]-3-(2-{4-[2-(2-o-oxy-1-indolyl)-1,3-thiazole- 5-yl]phenoxy}-5-pyrimidinyl)urea, (12) 1-[2-(1-methyl-1H-pyrazol-4-yl)-5-(trifluoromethyl)-3 -pyridyl]-3-(2-{4-[2-(2-o-oxy-1-piperidyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl) Urea, (13) 1-[1-(3,4-dimethylphenyl)-3-(2-methyl-2-propyl)-1H-pyrazol-5-yl]-3-(2 -{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (14) 1-[1 -(3,4- Methylphenyl)-3-(2-methyl-2-propyl)-1H-pyrazol-5-yl]-3-(2-{4-[2-(2-Sideoxy-1-) Piperidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (15) 1-[1-(2,3-dihydro-1H-indol-5-yl) )-3-(2-methyl-2-propyl)-1H-pyrazol-5-yl]-3-(2-{4-[2-(2-o-oxy-1-pyrrolidinyl)) -1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (16) 1-[1-(2,3-dihydro-1H-indol-5-yl)-3- (2-methyl-2-propyl)-1H-pyrazol-5-yl]-3-(2-{2-fluoro-4-[2-(2-o-oxy-1-pyrrolidinyl) -1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (17) 1-[1-(2,3-dihydro-1H-indol-5-yl)-3- (2-methyl-2-propyl)-1H-pyrazol-5-yl]-3-(2-{4-[2-(2-o-oxy-1-piperidyl)-1,3 -thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (18) 1-[1-(2,3-dihydro-1H-indol-5-yl)-3-(2-methyl 2-yl)-1H-pyrazol-5-yl]-3-(2-{3-fluoro-4-[2-(2-o-oxy-1-pyrrolidinyl)-1,3 -thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (19) 1-(2-{2-chloro-4-[2-(2-o-oxy-1-pyrrolidinyl) -1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-[1-(2,3-dihydro-1H-indol-5-yl)-3-(2-methyl Benzyl-2-propyl)-1H-pyrazol-5-yl]urea, (20) 1-[1-(2,3-dihydro-1 H-Indol-5-yl)-3-(2-methyl-2-propyl)-1H-pyrazol-5-yl]-3-(2-{4-[2-(2-trioxy) -1-azino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (21) 1-{1-[3-(hydroxymethyl)-4-methyl Phenyl]-3-(2-methyl-2-propyl)-1H-pyrazol-5-yl}-3-(2-{4-[2-(2-o-oxy-1-pyrrole) Pyridyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (22) 1-{1-[4-(hydroxymethyl)-3-methylphenyl] -3-(2-methyl-2-propyl)-1H-pyrazol-5-yl}-3-(2-{4-[2-(2-o-oxy-1-pyrrolidinyl)- 1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (23) 1-{3-(2-methyl-2-propyl)-1-[4-methyl- 3-(Trifluoromethyl)phenyl]-1H-pyrazol-5-yl}-3-(2-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3 -thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (24) 1-[3-(2-methyl-2-propyl)-1-[3,4,5-trimethyl Phenyl]-1H-pyrazol-5-yl]-3-(2-{4-[2-(2-o-oxy-1-piperidyl)-1,3-thiazol-5-yl] Phenoxy}-5-pyrimidinyl)urea, (25) 1-[3-(2-methyl-2-propyl)-1-[3,4,5-trimethylphenyl]-1H- Pyrazol-5-yl]-3-(2-{4-[2-(2-o-oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5- Pyrimidinyl)urea, (26) 1-[1-(4-fluorophenyl)-3-(2- Methyl-2-propyl)-1H-pyrazol-5-yl]-3-(2-{4-[2-(2-o-oxy-1-pyrrolidinyl)-1,3-thiazole- 5-yl]phenoxy}-5-pyrimidinyl)urea, (27) 1-[1-(4-methoxy-3,5-dimethylphenyl)-3-(2-methyl- 2-propyl)-1H-pyrazol-5-yl]-3-(2-{4-[2-(2-o-oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl) Phenoxy}-5-pyrimidinyl)urea, (28) 1-{3-(2-methyl-2-propyl)-1-[4-(trifluoromethyl)phenyl]-1H- Pyrazol-5-yl}-3-(2-{4-[2-(2-o-oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5- Pyrimidinyl)urea, (29) 1-[3-(2-methyl-2-propyl)-1-phenyl-1H-pyrazol-5-yl]-3-(2-{4-[2 -(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (30) 1-[1-(4-methyl Phenyl)-3-(2-methyl-2-propyl)-1H-pyrazol-5-yl]-3-(2-{4-[2-(2-o-oxy-1-pyrrolidine) -1,3-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (31) 1-[1-mesityl-3-(2-methyl-2-propyl) -1H-pyrazol-5-yl]-3-(2-{4-[2-(2-o-oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy }-5-pyrimidinyl)urea, (32) 1-[1-(2-methylphenyl)-3-(2-methyl-2-propyl)-1H-pyrazol-5-yl]- 3-(2-{4-[2-(2-Sideoxy-1-pyryla) Pyridyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (33) 1-[1-(2,3-dihydro-1-benzofuran-5- 3-(2-methyl-2-propyl)-1H-pyrazol-5-yl]-3-(2-{4-[2-(2-o-oxy-1-pyrrolidinyl) )-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (34) 1-[1-(2,3-dimethylphenyl)-3-(2-methyl Benzyl-2-propyl)-1H-pyrazol-5-yl]-3-(2-{4-[2-(2-o-oxy-1-pyrrolidinyl)-1,3-thiazole-5 -yl]phenoxy}-5-pyrimidinyl)urea, (35) 1-[1-(4-methoxyphenyl)-3-(2-methyl-2-propyl)-1H-pyridyl Zyrid-5-yl]-3-(2-{4-[2-(2-o-oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidine Urea, (36) 1-[1-(4-fluoro-2-methylphenyl)-3-(2-methyl-2-propyl)-1H-pyrazol-5-yl]-3 -(2-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (37)1 -[1-(2-fluorophenyl)-3-(2-methyl-2-propyl)-1H-pyrazol-5-yl]-3-(2-{4-[2-(2- Oxyloxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (38) 1-[1-(2-fluoro-3-methyl Phenyl)-3-(2-methyl-2-propyl)-1H-pyrazol-5-yl]-3-(2-{4-[2-(2-o-oxy-1-pyrrolidine) ))-1,3-thiazol-5-yl]phenoxy}-5- Pyridyl)urea, (39) 1-[1-(3-fluorophenyl)-3-(2-methyl-2-propyl)-1H-pyrazol-5-yl]-3-(2- {4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (40) 1-[1- (2-methylphenyl)-3-(2-methyl-2-propyl)-1H-pyrazol-5-yl]-3-(2-{4-[2-(2- oxooxy) 1-(piperidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (41)methyl 3-[3-(2-methyl-2-propyl -5-{[(2-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)amine Methyl hydrazino]amino}-1H-pyrazol-1-yl]benzoate, (42) N-{4-[3-(2-methyl-2-propyl)-5-{[ (2-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)aminomethylindenyl]amine }}-1H-pyrazol-1-yl]phenyl}acetamidine, (43) 1-[1-(1,3-benzophenanthrene) -5-5-yl)-3-(2-methyl-2-propyl)-1H-pyrazol-5-yl]-3-(2-{4-[2-(2- oxo-1) -pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (44) 1-[3-(2-methyl-2-propyl)-1- Phenyl-1H-pyrazol-5-yl]-3-(2-{4-[2-(2-o-oxy-1-piperidyl)-1,3-thiazol-5-yl]phenoxy }-5-pyrimidinyl)urea, (45) 1-[1-(2,3-dimethoxyphenyl)-3-(2-methyl-2-propyl)-1H-pyrazole- 5-yl]-3-(2-{4-[2-(2-o-oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl) Urea, (46) 1-[1-(2-fluoro-4-methoxyphenyl)-3-(2-methyl-2-propyl)-1H-pyrazol-5-yl]-3- (2-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (47)1- {1-[2-Fluoro-4-(trifluoromethyl)phenyl]-3-(2-methyl-2-propyl)-1H-pyrazole-5-yl}-3-(2-{ 4-[2-(2-Sideoxy-1-piperidyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (48) 1-[1-( 2-Chloro-4-methylphenyl)-3-(2-methyl-2-propyl)-1H-pyrazol-5-yl]-3-(2-{4-[2-(2- Oxo-1-piperidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (49) 1-[1-(2,5-dimethylbenzene 3-(2-methyl-2-propyl)-1H-pyrazole-5-yl]-3-(2 -{4-[2-(2-Sideoxy-1-piperidyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (50) 1-[1 -(2-fluorophenyl)-3-(2-methyl-2-propyl)-1H-pyrazol-5-yl]-3-(2-{4-[2-(2-trioxy) 1-(piperidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (51) 1-[1-(2-fluoro-4-methylphenyl) -3-(2-methyl-2-propyl)-1H-pyrazol-5-yl]-3-(2-{4-[2-(2-indolyl-1-piperidinyl)- 1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (52) 1-[1-(4-fluorophenyl)-3-(2-methyl-2-propyl -1H-pyrazol-5-yl]-3-(2-{4-[2-(2-o-oxy-1-piperidinyl)-1,3-thiazol-5-yl]phenoxy }-5-pyrimidinyl)urea, (53) 1-[1-(3-butoxyphenyl)-3-(2-methyl-2-propyl)-1H-pyrazol-5-yl] -3-(2-{4-[2-(2-Sideoxy-1-piperidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (54 1-[3-(2-methyl-2-propyl)-1-(4-propylphenyl)-1H-pyrazol-5-yl]-3-(2-{4-[2- (2-Sideoxy-1-piperidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (55)1-[1-(3-chloro-4) -methylphenyl)-3-(2-methyl-2-propyl)-1H-pyrazol-5-yl]-3-(2-{4-[2-(2-trioxy-1) -piperidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (56) 1-{3-( 2-methyl-2-propyl)-1-[4-(trifluoromethyl)phenyl]-1H-pyrazol-5-yl}-3- (2-{4-[2-(2- Oxo-1-piperidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (57) 1-[1-(4-methylphenyl)- 3-(2-methyl-2-propyl)-1H-pyrazol-5-yl]-3-(2-{4-[2-(2-o-oxy-1-piperidyl)-1 , 3-thiazole-5-yl]phenoxy}-5-pyrimidinyl)urea, (58) 1-[1-(3-methoxy-4-methylphenyl)-3-(2-methyl 2-yl)-1H-pyrazol-5-yl]-3-(2-{4-[2-(2-o-oxy-1-piperidyl)-1,3-thiazole-5 -yl]phenoxy}-5-pyrimidinyl)urea, (59) 1-[1-(3-methylphenyl)-3-(2-methyl-2-propyl)-1H-pyrazole -5-yl]-3-(2-{4-[2-(2-o-oxy-1-piperidyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl Urea, (60) 1-[1-(3,4-dihydro-2H-chromen-6-yl)-3-(2-methyl-2-propyl)-1H-pyrazole-5- 3-(2-{4-[2-(2-Sideoxy-1-piperidyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (61) 1-{1-[4-(3-Hydroxypropyl)phenyl]-3-(2-methyl-2-propyl)-1H-pyrazole-5-yl}-3-(2 -{4-[2-(2-Sideoxy-1-piperidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (62) 1-[1 -(3-methoxyphenyl)-3-(2-methyl-2-propyl)-1H-pyrazole-5- ]-3-(2-{4-[2-(2-Sideoxy-1-piperidyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, 63) 1-[1-(2,3-dihydro-1,4-benzoic acid -6-yl)-3-(2-methyl-2-propyl)-1H-pyrazol-5-yl]-3-(2-{4-[2-(2-trioxy-1) -piperidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (64) 1-[1-(2,5-dimethylphenyl)-3- (2-methyl-2-propyl)-1H-pyrazol-5-yl]-3-(2-{4-[2-(2-o-oxy-1-pyrrolidinyl)-1,3 -thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (65) 1-{1-[3-(2-hydroxyethyl)phenyl]-3-(2-methyl-2 -propyl)-1H-pyrazol-5-yl}-3-(2-{4-[2-(2-o-oxy-1-piperidyl)-1,3-thiazol-5-yl] Phenoxy}-5-pyrimidinyl)urea, (66) 1-[1-(3,5-dimethyl-4-propoxyphenyl)-3-(2-methyl-2-propyl -1H-pyrazol-5-yl]-3-(2-{4-[2-(2-o-oxy-1-piperidinyl)-1,3-thiazol-5-yl]phenoxy }-5-pyrimidinyl)urea, (67) 1-[1-(3-isopropylphenyl)-3-(2-methyl-2-propyl)-1H-pyrazol-5-yl] -3-(2-{4-[2-(2-Sideoxy-1-piperidyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (68 1-[1-(2,3-dihydro-1-benzofuran-5-yl)-3-(2-methyl-2-propyl)-1H-pyrazole-5-yl]-3 -(2-{4-[2-(2-Sideoxy-1-piperidyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (69)1 -[1-(2-chloro-6-methylphenyl)-3-(2-methyl-2-propyl) -1H-pyrazol-5-yl]-3-(2-{4-[2-(2-o-oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy} -5-pyrimidinyl)urea, (70) 1-[1-(3-fluoro-2-methylphenyl)-3-(2-methyl-2-propyl)-1H-pyrazole-5- 3-(2-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (71) 1-[1-(5-Fluoro-2-methylphenyl)-3-(2-methyl-2-propyl)-1H-pyrazole-5-yl]-3-(2- {4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (72) 1-[1- (2-ethylphenyl)-3-(2-methyl-2-propyl)-1H-pyrazol-5-yl]-3-(2-{4-[2-(2- oxooxy) -1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (73) 1-[1-(2-methylphenyl)-3-( 2-methyl-2-propyl)-1H-pyrazol-5-yl]-3-(2-{4-[2-(2-o-oxy-1-indolyl)-1,3- Thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (74) 1-[1-(2-chlorophenyl)-3-(2-methyl-2-propyl)-1H- Pyrazol-5-yl]-3-(2-{4-[2-(2-o-oxy-1-piperidyl)-1,3-thiazol-5-yl]phenoxy}-5- Pyrimidinyl)urea, (75) 1-{3-(2-methyl-2-propyl)-1-[3-(trifluoromethyl)phenyl]-1H-pyrazole-5-yl}- 3-(2-{4-[2-(2-Sideoxy-1-piperidyl)-1,3-thiazole-5- (phenoxy}-5-pyrimidinyl)urea, (76) 1-[1-(3-ethylphenyl)-3-(2-methyl-2-propyl)-1H-pyrazole- 5-yl]-3-(2-{4-[2-(2-o-oxy-1-piperidyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl) Urea, (77) 1-[1-(2-chloro-4-fluorophenyl)-3-(2-methyl-2-propyl)-1H-pyrazole-5-yl]-3-(2 -{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (78)1-[1 -(4-chloro-2-methylphenyl)-3-(2-methyl-2-propyl)-1H-pyrazol-5-yl]-3-(2-{4-[2-( 2-sided oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (79) 1-[1-(3-methoxy- 2,4-Dimethylphenyl)-3-(2-methyl-2-propyl)-1H-pyrazol-5-yl]-3-(2-{4-[2-(2- side Oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (80) 1-[1-(2-methoxyphenyl)- 3-(2-methyl-2-propyl)-1H-pyrazol-5-yl]-3-(2-{4-[2-(2-o-oxy-1-pyrrolidinyl)-1 , 3-thiazole-5-yl]phenoxy}-5-pyrimidinyl)urea, (81) 1-[1-(2-fluoro-5-methylphenyl)-3-(2-methyl- 2-propyl)-1H-pyrazol-5-yl]-3-(2-{4-[2-(2-o-oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl) Phenoxy}-5-pyrimidinyl)urea, (82) 1-[1-(2-chloro -5-methylphenyl)-3-(2-methyl-2-propyl)-1H-pyrazol-5-yl]-3-(2-{4-[2-(2-)oxy -1-pyrrolidyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (83) 1-[1-(2-fluoro-4-methylphenyl) -3-(2-methyl-2-propyl)-1H-pyrazol-5-yl]-3-(2-{4-[2-(2-o-oxy-1-pyrrolidinyl)- 1,3-thiazole-5-yl]phenoxy}-5-pyrimidinyl)urea, (84) 1-[1-(3-fluoro-2,4-dimethylphenyl)-3-(2 -methyl-2-propyl)-1H-pyrazol-5-yl]-3-(2-{4-[2-(2-o-oxy-1-pyrrolidinyl)-1,3-thiazole -5-yl]phenoxy}-5-pyrimidinyl)urea, (85) 1-[1-(2-chloro-4-methylphenyl)-3-(2-methyl-2-propyl -1H-pyrazol-5-yl]-3-(2-{4-[2-(2-o-oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy }-5-pyrimidinyl)urea, (86)4-[3-(2-methyl-2-propyl)-5-{[(2-{4-[2-(2-trioxy-1) -pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)aminomethylindenyl]amino}-1H-pyrazol-1-yl]benzenesulfonamide (87) 1-[1-(2-Methylphenyl)-3-(2-methyl-2-propyl)-1H-pyrazol-5-yl]-3-(6-{4-[ 2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-3-pyridyl)urea, (88) 1-(5-methyl-6 -{4-[2-(2-Sideoxy-1-pyrrolidine) )-1,3-thiazol-5-yl]phenoxy}-3-pyridyl)-3-[1-(2-methylphenyl)-3-(2-methyl-2-propyl) -1H-pyrazol-5-yl]urea, (89) 1-[1-(1-methyl-1H-indol-5-yl)-3-(2-methyl-2-propyl)- 1H-pyrazol-5-yl]-3-(2-{4-[2-(2-o-oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}- 5-pyrimidinyl)urea, (90) 1-[1-(1-methyl-1H-indazol-5-yl)-3-(2-methyl-2-propyl)-1H-pyrazole- 5-yl]-3-(2-{4-[2-(2-o-oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl) Urea, (91) 1-[1-(2-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl]-3-(2-{4-[2-( 2-sided oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (92) 1-[1-(3,4-dimethyl Phenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl]-3-(2-{4-[2-(2-o-oxy-1-pyrrolidinyl)-1 , 3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (93) 1-[3-(1,1-difluoroethyl)-1-(2-methylphenyl) -1H-pyrazol-5-yl]-3-(2-{4-[2-(2-o-oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy} -5-pyrimidinyl)urea, (94) 1-[1-(4-fluorophenyl)-3-(trifluoromethyl)-1H-pyrazole-5-yl]-3-(2-{4 -[2-(2-Sideoxy-1-pyrrolidinyl)-1,3- (5)1-[1-(2-methylphenyl)-3-(trifluoromethyl)-1H-pyrazole-5 -yl]-3-(2-{4-[2-(2-o-oxy-1-piperidyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea ,(96)1-[3-(1,1-Difluoroethyl)-1-(2-methylphenyl)-1H-pyrazol-5-yl]-3-(2-{4-[ 2-(2-Sideoxy-1-piperidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (97) 1-(3-cyclopropyl- 1-phenyl-1H-pyrazol-5-yl)-3-(2-{4-[2-(2-o-oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl] Phenoxy}-5-pyrimidinyl)urea, (98) 1-(3-isopropyl-1-phenyl-1H-pyrazol-5-yl)-3-(2-{4-[2- (2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (99) 1-[1-(6-methoxy -3-pyridyl)-3-(2-methyl-2-propyl)-1H-pyrazol-5-yl]-3-(2-{4-[2-(2-trioxy-1) -pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (100) 1-[3-(2-methyl-2-propyl)-1- (6-methyl-3-pyridyl)-1H-pyrazol-5-yl]-3-(2-{4-[2-(2-o-oxy-1-pyrrolidinyl)-1,3 -thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (101) 1-[3-(2-methyl-2-propyl)-1-(3-pyridyl)-1H- Pyrazol-5-yl]-3-(2-{4-[2-( 2-sided oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (102) 1-[1-(6-isopropoxy -3-pyridyl)-3-(2-methyl-2-propyl)-1H-pyrazol-5-yl]-3-(2-{4-[2-(2-trioxy-1) -pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (103) 1-[3-(2-methyl-2-propyl)-1- (6-methyl-3-pyridyl)-1H-pyrazol-5-yl]-3-(2-{4-[2-(2-o-oxy-1-piperidyl)-1,3 -thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (104) 1-[3-(2-methyl-2-propyl)-1-(3-pyridyl)-1H- Pyrazol-5-yl]-3-(2-{4-[2-(2-o-oxy-1-piperidyl)-1,3-thiazol-5-yl]phenoxy}-5- Pyrimidinyl)urea, (105) 1-(2-{4-[2-(2-o-oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5- Pyrimidinyl)-3-[2-(4-pyridyl)-5-(trifluoromethyl)phenyl]urea, (106) 1-[2-(4-morpholinyl)-5-(trifluoro Methyl)phenyl]-3-(2-{4-[2-(2-o-oxy-1-piperidyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidine Urea, (107) 1-[2-(4-methyl-1-piperidin 5-(3-trifluoromethyl)phenyl]-3-(2-{4-[2-(2-o-oxy-1-piperidyl)-1,3-thiazol-5-yl] Phenoxy}-5-pyrimidinyl)urea, (108) 1-[3-(2-methyl-2-propyl)-1-(1,2,3,4-tetrahydro-2-naphthyl -1H-pyrazol-5-yl]-3-(2-{4-[2-(2-o-oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy }-5-pyrimidinyl)urea, (109) 1-[3-(2-methyl-2-propyl)-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole- 5-yl]-3-(2-{4-[2-(2-o-oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl) Urea, (110) 1-[1-cyclohexyl-3-(2-methyl-2-propyl)-1H-pyrazol-5-yl]-3-(2-{4-[2-(2) -Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (111)1-[2-cyclohexyl-5-(trifluoro) Methyl)-3-pyridyl]-3-(2-{4-[2-(2-o-oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}- 5-pyrimidinyl)urea, (112)1-[2-(3,4-dimethylphenyl)-5-methyl-3-pyridyl]-3-(2-{4-[2-( 2-sided oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (113) 1-[2-(3,4-dimethyl Phenylphenyl)-3-pyridyl]-3-(2-{4-[2-(2-o-oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy} -5-pyrimidine Urea, (114) 1-(3-isopropyl-1-phenyl-1H-pyrazol-5-yl)-3-(2-{4-[2-(2-Sideoxy-1-) Pyrrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (115) 1-(2-{4-[2-(2-Sideoxy-1-) Pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl-3-[2-(3-pyridyl)-5-(trifluoromethyl)phenyl]urea , (116) 1-(6-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-3-pyridyl)- 3-[2-(4-Pyridinyl)-5-(trifluoromethyl)phenyl]urea, (117)1-[6'-methyl-5-(trifluoromethyl)-2,3' -dipyridin-3-yl]-3-(6-{4-[2-(2-o-oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-3 -pyridyl)urea, (118) 1-(6-{4-[2-(2-o-oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-3 -pyridyl)-3-[2-(3-pyridyl)-5-(trifluoromethyl)phenyl]urea, (119) 1-(6-{4-[2-(2-trioxy) -1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-3-pyridyl)-3-[2-phenyl-5-(trifluoromethyl)-3-pyridyl Urea, (120) 1-(6-{4-[2-(2-o-oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-3-pyridyl -3-[5-(Trifluoromethyl)-2,4'-dipyridin-3-yl]urea, (121)1-[2-(4-methylphenyl)-5-( Trifluoromethyl)-3-pyridyl]-3-(6-{4-[2-(2-o-oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy }-3-pyridyl)urea, (122) 1-[2-(6-methyl-3-pyridyl)-5-(trifluoromethyl)phenyl]-3-(6-{4-[ 2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-3-pyridyl)urea, (123) 1-[1-oxoanion group ( Oxixo)-2-phenyl-5-(trifluoromethyl)-3-pyridyl]-3-(2-{4-[2-(2-o-oxy-1-pyrrolidinyl)-1, 3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (124) 1-(6-{4-[2-(2-o-oxy-1-pyrrolidinyl)-1, 3-thiazol-5-yl]phenoxy}-3-pyridyl)-3-{5-(trifluoromethyl)-2-[6-(trifluoromethyl)-3-pyridyl]phenyl Urea, (125) 1-[2-(6-methyl-3-pyridyl)-5-(trifluoromethyl)phenyl]-3-(2-{4-[2-(2- side) Oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (126) 1-(6-{4-[2-(2- side Oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-3-pyridyl)-3-[5-(trifluoromethyl)-2,3'-dipyridine -3-yl]urea, (127) 1-[2-(6-methoxy-3-pyridyl)-5-(trifluoromethyl)phenyl]-3-(6-{4-[2 -(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-3-pyridyl) , (128) 1-[2-(3-hydroxyphenyl)-5-(trifluoromethyl)-3-pyridyl]-3-(2-{4-[2-(2- oxo-) 1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (129) 1-(2-{4-[2-(2-sideoxy)- 1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl-3-[5-(trifluoromethyl)-2,3'-dipyridine-3- Urea, (130) 1-[2-(1-oxanyl-4-pyridyl)-5-(trifluoromethyl)phenyl]-3-(6-{4-[2-(2) -Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-3-pyridyl)urea, (131) 1-(6-{4-[2-(2 -Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-3-pyridyl)-3-[4-(trifluoromethyl)-2-biphenyl Urea, (132) 1-[2-(4-hydroxyphenyl)-5-(trifluoromethyl)-3-pyridyl]-3-(2-{4-[2-(2- side oxygen) (1-pyridyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (133) 1-[2-(1-oxananyl-4-pyridyl) -5-(Trifluoromethyl)phenyl]-3-(2-{4-[2-(2-o-oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]benzene Oxy}-5-pyrimidinyl)urea, (134) 1-[2-(1-oxanyl-3-pyridyl)-5-(trifluoromethyl)phenyl]-3-(6-{ 4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy} -3-pyridyl)urea, (135) 1-[2-(1-oxanyl-3-pyridyl)-5-(trifluoromethyl)phenyl]-3-(2-{4-[ 2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (136) 1-[2-(2-A Oxyphenyl)-5-(trifluoromethyl)-3-pyridyl]-3-(2-{4-[2-(2-o-oxy-1-pyrrolidinyl)-1,3- Thiazol-5-yl]phenoxy}-5-pyrimidinyl urea, (137) 1-[2-(3-methoxyphenyl)-5-(trifluoromethyl)-3-pyridyl} 3-(2-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (138) 1-[2-(2-hydroxyphenyl)-5-(trifluoromethyl)-3-pyridyl]-3-(2-{4-[2-(2-o-oxy-1-pyrrolidine) -1,3-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (139) 1-(1-oxoanion-6-{4-[2-(2- side oxygen) -ylpyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-3-pyridyl)-3-[2-phenyl-5-(trifluoromethyl)-3-pyridine Urea, (140) 1-[2-(4-methoxyphenyl)-5-(trifluoromethyl)-3-pyridyl]-3-(2-{4-[2-(2) -Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (141) 1-[2-cyclohexyl-5-(trifluoro Methyl)-3-pyridyl]-3-(2-{4-[2-(2-o-oxy-1-piperidinyl) )-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (142) 1-[3-(2-methyl-2-propyl)-1-phenyl-1H -pyrazol-5-yl]-3-(6-{4-[2-(2-o-oxy-1-piperidinyl)-1,3-thiazol-5-yl]phenoxy}-3 -pyridyl)urea, (143) 1-(6-{4-[2-(2-o-oxy-1-piperidinyl)-1,3-thiazol-5-yl]phenoxy}-3 -pyridyl)-3-[2-phenyl-5-(trifluoromethyl)-3-pyridyl]urea, (144) 1-(6-{4-[2-(2-sideoxy)- 1-piperidinyl)-1,3-thiazol-5-yl]phenoxy}-3-pyridyl)-3-[2-(4-pyridyl)-5-(trifluoromethyl)phenyl Urea, (145) 1-(6-{4-[2-(2-o-oxy-1-piperidyl)-1,3-thiazol-5-yl]phenoxy}-3-pyridyl -3-[2-(3-pyridyl)-5-(trifluoromethyl)phenyl]urea, (146) 1-(2-{4-[2-(2- oxo-1-) Piperidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl-3-[5-(trifluoromethyl)-2,4'-dipyridin-3-yl] Urea, (147) 1-(2-{4-[2-(2-o-oxy-1-piperidyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl) -3-[2-(3-pyridyl)-5-(trifluoromethyl)phenyl]urea, (148) 1-(2-{4-[2-(2- oxo-l-piper Pyridyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl-3-[5-(trifluoromethyl)-2,3'-dipyridin-3-yl]urea , (149) 1-(2 -{4-[2-(2-Sideoxy-1-piperidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-[2-(4- Pyridyl)-5-(trifluoromethyl)phenyl]urea, (150) 1-[2-(6-methyl-3-pyridyl)-5-(trifluoromethyl)phenyl]-3 -(2-{4-[2-(2-Sideoxy-1-piperidyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (151) Phosphoric acid Dihydro 3-[3-{[(2{4-[2-(2-o-oxy-1-pyrrolidinyl)-1,3-thiazol-5-pyrimidinyl]aminomethylindenyl}-amino group -5-(Trifluoromethyl)-2-pyridyl]phenyl, (152) 1-[6-({6-[2-(2-o-oxy-1-pyrrolidinyl)-1, 3-thiazol-5-yl]-3-pyridyl}oxy)-3-pyridyl]-3-[2-phenyl-5-(trifluoromethyl)-3-pyridyl]urea, (153 1-[2-(4-{2-[(4S)-4-hydroxy-2-oxo-l-pyrrolidinyl]-1,3-thiazol-5-yl}phenoxy)-5 -pyrimidinyl]-3-[2-phenyl-5-(trifluoromethyl)-3-pyridyl]urea, (154) 1-(2-{2-fluoro-4-[2-(2- Oxyloxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl-3-[2-phenyl-5-(trifluoromethyl)-3 -pyridyl]urea, (155) 1-(2-{2-fluoro-4-[2-(2-o-oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy }-5-pyrimidinyl-3-[2-(3-pyridyl)-5-(trifluoromethyl)phenyl]urea, (156) 1-[ 2-(1-oxanyl-3-pyridyl)-5-(trifluoromethyl)-3-pyridyl]-3-(6-{4-[2-(2- oxo-1-) Pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-3-pyridyl)urea, (157)1-[2-(1-oxanyl-3-pyridyl)-5- (trifluoromethyl)-3-pyridyl]-3-(2-{4-[2-(2-o-oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy }}-5-pyrimidinyl)urea, (158) 1-(6-{2-fluoro-4-[2-(2-o-oxy-1-pyrrolidinyl)-1,3-thiazole-5- (Phenoxy)-3-pyridyl)-3-[2-phenyl-5-(trifluoromethyl)-3-pyridyl]urea, (159) 1-(6-{2-fluoro- 4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-3-pyridyl)-3-[2-(3-pyridyl) -5-(Trifluoromethyl)phenyl]urea, (160) 1-[2-(2-methyl-4-pyridyl)-5-(trifluoromethyl)phenyl]-3-( 2-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (161) 1-( 2-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-[2-(4 -piperidinyl)-5-(trifluoromethyl)phenyl]urea, (162) 1-(2-{4-[2-(2-o-oxy-1-pyrrolidinyl)-1,3 -thiazol-5-yl]phenoxy}-5-pyrimidinyl-3-[2-(1,2,3,6-tetrahydro-4-pyridine 5-(3-trifluoromethyl)phenyl]urea, (163) 1-(4-methyl-6-{4-[2-(2-o-oxy-1-pyrrolidinyl)-1 , 3-thiazol-5-yl]phenoxy}-3-pyridyl)-3-[2-phenyl-5-(trifluoromethyl)-3-pyridyl]urea, (164)1-( 4-methyl-6-{4-[2-(2-o-oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-3-pyridyl)-3- [2-(3-Pyridinyl)-5-(trifluoromethyl)phenyl]urea, (165) 1-[2-(1-methyl-4-piperidinyl)-5-(trifluoromethyl) Phenyl]-3-(2-{4-[2-(2-o-oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl Urea, (166) 1-(2-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl -3-[2-(1H-pyrazol-3-yl)-5-(trifluoromethyl)phenyl]urea, (167) 1-(2-methyl-6-{4-[2- (2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-3-pyridyl)-3-[2-(3-pyridyl)-5-( Trifluoromethyl)phenyl]urea, (168) 1-(2-methyl-6-{4-[2-(2-o-oxy-1-pyrrolidinyl)-1,3-thiazole-5 -yl]phenoxy}-3-pyridyl)-3-[2-phenyl-5-(trifluoromethyl)-3-pyridyl]urea, (169) 1-[2-(1H-imidazole -1-yl)-5-(trifluoromethyl)phenyl]-3-(2-{4-[2-(2-o-oxy-1-pyrrolidinyl)-1,3-thiazide -5-yl]phenoxy}-5-pyrimidinyl)urea, (170) 1-(2-{4-[2-(2-methyl-5-oxo-l-pyrrolidinyl)- 1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-[2-phenyl-5-(trifluoromethyl)-3-pyridyl]urea, (171) 1- (2-{4-[2-(2-Methyl-5-oxo-l-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3 -[2-(3-pyridyl)-5-(trifluoromethyl)phenyl]urea, (172) 1-[5-(2-methyl-2-propyl)-2-(3-pyridine Phenyl]-3-(2-{4-[2-(2-o-oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl Urea, (173) 1-(5-methyl-6-{4-[2-(2-o-oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy} -3-pyridyl)-3-[2-phenyl-5-(trifluoromethyl)-3-pyridyl]urea, (174) 1-(5-methyl-6-{4-[2- (2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-3-pyridyl)-3-[2-(3-pyridyl)-5-( Trifluoromethyl)phenyl]urea, (175) 1-[2-(1-methyl-6-o-oxy-1,6-dihydro-3-pyridyl)-5-(trifluoromethyl Phenyl]-3-(2-{4-[2-(2-o-oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl) Urea, (176) 1-[2-(6-o-oxy-1,6-dihydro-3-pyridyl)-5-(trifluoromethyl)phenyl]- 3-(2-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (177) 1-[5-(3-oxetanyl)-2-phenyl-3-pyridyl]-3-(2-{4-[2-(2-o-oxy-1-pyrrolidinyl) )-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (178) 1-(2-{4-[2-(2-Sideoxy-1-nitrogen heterocycle) Butyryl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl-3-[2-(3-pyridyl)-5-(trifluoromethyl)phenyl]urea ,(179)1-[5-(3-oxetanyl)-2-(3-pyridyl)phenyl-]-3-(2-{4-[2-(2-)oxy -1-pyrrolidyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (180) 1-(2-{3-methyl-4-[2-( 2-sided oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl-3-[2-(3-pyridyl)-5-(three Fluoromethyl)phenyl]urea, (181) 1-[2-(4-{2-[4-(hydroxymethyl)-2-oxo-l-pyrrolidinyl]-1,3-thiazole -5-yl}phenoxy)-5-pyrimidinyl]-3-[2-(3-pyridyl)-5-(trifluoromethyl)phenyl]urea, (182) 1-[2-( {6-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]-3-pyridyl}oxy)-5-pyrimidinyl]-3-[2 -(3-pyridyl)-5-(trifluoromethyl)phenyl]urea, (183) 1-[2-(3-oxetanyl)-5-( Trifluoromethyl)phenyl]-3-(2-{4-[2-(2-o-oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5 -pyrimidinyl)urea, (184) 1-(2-{4-[2-(2-o-oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5 -pyrimidinyl-3-[2-(1H-pyrazol-1-yl)-5-(trifluoromethyl)phenyl]urea, (185) 1-[5-fluoro-2-(1H-imidazole -1-yl)phenyl]-3-(2-{4-[2-(2-o-oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5 -pyrimidyl)urea, (186) 1-[2-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl]-3-(2-{4-[ 2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (187) 1-(2-{4-[ 2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-[2-(1H-1,2,3 -Triazol-1-yl)-5-(trifluoromethyl)phenyl]urea, (188) 1-[2-(4-{2-[3-(2-hydroxy-2-propyl)- 2-Phenoxy-1-pyrrolidinyl]-1,3-thiazol-5-yl}phenoxy)-5-pyrimidinyl]-3-[2-(3-pyridyl)-5-(III Fluoromethyl)phenyl]urea, (189) 1-[2-(2-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl]-3-(2-{ 4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (190)1-[2-( 1H- Zin-1-yl)-5-(trifluoromethyl)phenyl]-3-[2-({6-[2-(2-oxo-1-pyrrolidinyl)-1,3-thiazole) -5-yl]-3-pyridyl}oxy)-5-pyrimidinyl]urea, (191) 1-(2-{4-[2-(2-o-oxy-1-pyrrolidinyl)- 1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl-3-[2-(4H-1,2,4-triazol-4-yl)-5-(trifluoromethyl Phenyl]urea, (192) 1-[6'-methyl-5-(trifluoromethyl)-2,3'-dipyridin-3-yl]-3-(2-{4-[2 -(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (193)1-[2-(4-{2 -[3-(2-hydroxy-2-propyl)-2-oxo-l-pyrrolidinyl]-1,3-thiazol-5-yl}phenoxy)-5-pyrimidinyl]-3 -[2-Phenyl-5-(trifluoromethyl)-3-pyridyl]urea, (194) 1-[5-fluoro-2-(3-pyridyl)phenyl]-3-(2- {4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (195) 1-(5- Methoxy-6-{4-[2-(2-o-oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-3-pyridyl)-3-[ 2-phenyl-5-(trifluoromethyl)-3-pyridyl]urea, (196) 1-[2-(2-methyl-3-pyridyl)-5-(trifluoromethyl)benzene 3-(2-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl Urea, (197) 1-[2-(4-methyl-3-pyridyl)-5-(trifluoromethyl)phenyl]-3-(2-{4-[2-(2- side) Oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (198) 1-(5-fluoro-2,3'-dipyridine- 3-yl)-3-(2-{4-[2-(2-o-oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl) Urea, (199) 1-[2-(5-methyl-3-pyridyl)-5-(trifluoromethyl)phenyl]-3-(2-{4-[2-(2- side oxygen) (1-pyridyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (200) 1-[5-fluoro-2-(4-pyridyl)benzene 3-(2-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (201) 1-[2-(1-Methyl-1H-imidazol-4-yl)-5-(trifluoromethyl)-3-pyridyl]-3-(2-{4-[2-( 2-sided oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (202) 1-(2-{4-[2-( 2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-[5-(trifluoromethyl)-2,2' -dipyridin-3-yl]urea, (203) 1-[5-fluoro-2-(2-pyridyl)phenyl]-3-(2-{4-[2-(2- oxo-) 1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, or (204)1-[2-cyclopropyl-5-(trifluoromethyl) Benzyl-3-pyridyl]-3-(2-{4-[2-(2-o-oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5 - Pyrimidinyl) urea, a salt thereof, an N-oxide thereof, a solvate thereof or such a prodrug.

通式(I)表示之化合物中，通式(I-2-a)表示之化合物更好為下述通式(I-2-a-1)或通式(I-2-a-2)表示之化合物、其鹽、其N- 氧化物、其溶劑化物或該等之前驅藥。 In the compound represented by the formula (I), the compound represented by the formula (I-2-a) is more preferably a compound of the following formula (I-2-a-1) or formula (I-2-a-2). a compound represented, a salt thereof, and a N- An oxide, a solvate thereof or such a precursor.

(式中，ra表示0至3之整數，t表示0至4之整數，其他符號與上述[1]及[6]記載之符號同意義。)。 (wherein, ra represents an integer of 0 to 3, and t represents an integer of 0 to 4, and other symbols have the same meaning as the symbols described in the above [1] and [6].).

通式(I)表示之化合物中，通式(I-2-b)表示之化合物更好為下述通式(I-2-b-1)或通式(I-2-b-2)表示之化合物、其鹽、其N-氧化物、其溶劑化物或該等之前驅藥。 In the compound represented by the formula (I), the compound represented by the formula (I-2-b) is more preferably a formula (I-2-b-1) or a formula (I-2-b-2) A compound, a salt thereof, an N-oxide thereof, a solvate thereof, or such a prodrug.

(式中，ra表示0至3之整數，t表示0至4之整數，其他符號與上述[1]及[6]記載之符號同意義。)。 (wherein, ra represents an integer of 0 to 3, and t represents an integer of 0 to 4, and other symbols have the same meaning as the symbols described in the above [1] and [6].).

通式(I)表示之化合物中，通式(I-2-a-1)表示之化合物、通式(I-2-a-2)表示之化合物、通式(I-2-b-1)表示之化合物或通式(I-2-b-2)表示之化合物較好為該等通式之環Cy2為C3至10單環式碳環或5至10員單環式雜環或二環式雜環，R1為(1)鹵素原子、(2)C1至4烷基、(3)經鹵素原子取代之C1至4烷基、(4)環丙基、(5)環丁基、(6)經鹵素原子取代之環丙基、(7)經鹵素原子取代之環丁基、(8)氧雜環丁烷基及(9)經甲基取代之氧雜環丁烷基，R3為氟原子、氯原子、甲基、三氟甲基及甲氧基，R4為氟原子、氯原子、甲基、三氟甲基及甲氧基，R6為(1)鹵素原子、(2)羥基、(3)C1至4烷基、(4)經鹵素原子取代之C1至4烷基、(5)經羥基取代之C1至4烷基、(6)C3至6環烷基、(7)C1至4烷氧基、(8)羧基、(9)-CO2(C1 至4烷基)、(10)乙醯基醯胺基、(11)膦醯基氧基及(12)磺醯胺基，R7為C1至6烷基，X為鍵結或氧原子，pa為0至2之整數，pb為0至2之整數，q為0至2之整數，ra為0至1之整數及t為0至2之整數表示之化合物、其鹽、其N-氧化物、其溶劑化物或該等之前驅藥，更好為該等通式之環Cy2為環丙烷、苯、環己烷、茚烷、四氫萘、吡喃、呋喃、噻吩、吡咯、異唑、唑、異噻唑、噻唑、吡唑、咪唑、三唑、吡啶、吡啶酮、嗒、嘧啶、吡、四氫吡喃、四氫噻喃、哌啶、嗎啉、硫代嗎啉、四氫吡啶、苯并二烷、哌、全氫茚、二氫苯并呋喃、二氫苯并噻吩、吲哚啉、苯并二茂、苯并硫醇、二氫苯并唑、二氫苯并噻唑、色滿、硫代色滿、四氫喹啉、二氫苯并二英、二氫苯并氧硫雜環己二烯、二氫苯并、吲哚、苯并呋喃、苯并噻吩、吲唑及四氫萘，R1為(1)鹵素原子、(2)C1至4烷基、(3)經鹵素原子取代之C1至4烷基、(4)環丙基、(5)環丁基、(6)經鹵素原子取代之環丙基、(7)經鹵素原子取代之環丁基、(8)氧雜環丁烷基及(9)經甲基取代之氧雜環丁烷基，R3為氟原子、氯原子、甲基、三氟甲基及甲氧基，R4為氟原子、氯原子、甲基、三氟甲基及甲氧基，R6為(1)鹵素原子、(2)羥基、(3)C1至4烷基、(4)經鹵素原子取代之C1至4烷基、(5)經羥基取代之C1至4烷基、(6)C3至6環烷基、(7)C1至4烷氧基、(8)羧基、(9)-CO2(C1至4烷基)、(10)乙醯基醯胺基、(11)膦醯基氧基及(12)磺醯胺基，R7為C1至6烷基，X為鍵結或氧原子，pa為0至2之整數，pb為0至2之整數，q為0至2之整數，ra為0至1之整數及t為0至2之整數表示之化合物、其鹽、其N-氧化物、其溶劑化物或該等之前驅藥，更好為該等通式 之環Cy2為苯、吡啶、吡唑、咪唑及三唑，R1為(1)鹵素原子、(2)C1至4烷基、(3)經鹵素原子取代之C1至4烷基、(4)環丙基、(5)環丁基、(6)經鹵素原子取代之環丙基、(7)經鹵素原子取代之環丁基、(8)氧雜環丁烷基及(9)經甲基取代之氧雜環丁烷基，R3為氟原子、氯原子、甲基、三氟甲基及甲氧基，R4為氟原子、氯原子、甲基、三氟甲基及甲氧基，R6為(1)鹵素原子、(2)羥基、(3)C1至4烷基、(4)經鹵素原子取代之C1至4烷基、(5)經羥基取代之C1至4烷基、(6)C3至6環烷基、(7)C1至4烷氧基、(8)羧基、(9)-CO2(C1至4烷基)、(10)乙醯基醯胺基、(11)膦醯基氧基及(12)磺醯胺基，R7為C1至6烷基，X為鍵結或氧原子，pa為0至2之整數，pb為0至2之整數，q為0至2之整數，ra為0至1之整數及t為0至2之整數表示之化合物、其鹽、其N-氧化物、其溶劑化物或該等之前驅藥。 In the compound represented by the formula (I), the compound represented by the formula (I-2-a-1), the compound represented by the formula (I-2-a-2), and the formula (I-2-b-1) The compound represented by the formula or the compound represented by the formula (I-2-b-2) is preferably a ring of the formula: Cy 2 is a C3 to 10 monocyclic carbocyclic ring or a 5 to 10 membered monocyclic heterocyclic ring or a bicyclic heterocyclic ring, R 1 is (1) a halogen atom, (2) a C1 to 4 alkyl group, (3) a C1 to 4 alkyl group substituted by a halogen atom, (4) a cyclopropyl group, (5) a cyclobutene a group, (6) a cyclopropyl group substituted with a halogen atom, (7) a cyclobutyl group substituted with a halogen atom, (8) an oxetanyl group, and (9) a methyl substituted oxetanyl group R 3 is a fluorine atom, a chlorine atom, a methyl group, a trifluoromethyl group and a methoxy group, R 4 is a fluorine atom, a chlorine atom, a methyl group, a trifluoromethyl group and a methoxy group, and R 6 is a halogen atom (1). Atom, (2) hydroxy, (3) C1 to 4 alkyl, (4) C1 to 4 alkyl substituted by halogen atom, (5) C1 to 4 alkyl substituted by hydroxy group, (6) C3 to 6 ring Alkyl, (7) C1 to 4 alkoxy, (8) carboxyl, (9)-CO 2 (C1 to 4 alkyl), (10) ethyl hydrazide, (11) phosphinyloxy and (12) sulfonic group, R 7 is a C1 to C6 alkyl, X is a bond or an oxygen atom, pa is 0 An integer of 2, pb is an integer from 0 to 2, q is an integer from 0 to 2, ra is an integer from 0 to 1, and t is an integer represented by an integer from 0 to 2, a salt thereof, an N-oxide thereof, and a solvent thereof Or such a prodrug, more preferably the ring of the formula Cy 2 is cyclopropane, benzene, cyclohexane, decane, tetrahydronaphthalene, pyran, furan, thiophene, pyrrole, iso Azole, Oxazole, isothiazole, thiazole, pyrazole, imidazole, triazole, pyridine, pyridone, anthracene Pyrimidine, pyridyl , tetrahydropyran, tetrahydrothiopyran, piperidine, morpholine, thiomorpholine, tetrahydropyridine, benzodiazepine Alkane , all hydroquinone, dihydrobenzofuran, dihydrobenzothiophene, porphyrin, benzodiazepine Mao, benzo Mercaptan, dihydrobenzo Azole, dihydrobenzothiazole, chroman, thiochroman, tetrahydroquinoline, dihydrobenzo English, dihydrobenzothiazepine, dihydrobenzo , hydrazine, benzofuran, benzothiophene, oxazole and tetrahydronaphthalene, R 1 is (1) a halogen atom, (2) a C1 to 4 alkyl group, and (3) a C1 to 4 alkyl group substituted by a halogen atom. (4) cyclopropyl, (5) cyclobutyl, (6) a cyclopropyl group substituted with a halogen atom, (7) a cyclobutyl group substituted with a halogen atom, (8) oxetanyl group and 9) a methyl-substituted oxetanyl group, R 3 is a fluorine atom, a chlorine atom, a methyl group, a trifluoromethyl group and a methoxy group, and R 4 is a fluorine atom, a chlorine atom, a methyl group, a trifluoromethyl group. And methoxy, R 6 is (1) halogen atom, (2) hydroxyl group, (3) C1 to 4 alkyl group, (4) C1 to 4 alkyl group substituted by halogen atom, (5) substituted by hydroxy group C1 to 4 alkyl, (6) C3 to 6 cycloalkyl, (7) C1 to 4 alkoxy, (8) carboxyl, (9)-CO 2 (C1 to 4 alkyl), (10) ethyl hydrazine The base amino group, (11) phosphinyloxy group and (12) sulfonylamino group, R 7 is a C1 to 6 alkyl group, X is a bond or an oxygen atom, pa is an integer of 0 to 2, and pb is 0. An integer of 2, q is an integer from 0 to 2, ra is an integer from 0 to 1, and t is a compound represented by an integer from 0 to 2, a salt thereof, an N-oxide thereof, a solvate thereof, or such a prodrug ring, the better for such formula Cy 2 Benzene, pyridine, pyrazole, imidazole, and triazole, R 1 is (1) a halogen atom, (2) a C1 to C4 alkyl, (3) of a C1 to C4 alkyl substituted with halogen atom, (4) cyclopropyl And (5) a cyclobutyl group, (6) a cyclopropyl group substituted with a halogen atom, (7) a cyclobutyl group substituted with a halogen atom, (8) an oxetanyl group, and (9) a methyl group substituted Oxetane, R 3 is a fluorine atom, a chlorine atom, a methyl group, a trifluoromethyl group and a methoxy group, and R 4 is a fluorine atom, a chlorine atom, a methyl group, a trifluoromethyl group and a methoxy group, R 6 is (1) a halogen atom, (2) a hydroxyl group, (3) a C1 to 4 alkyl group, (4) a C1 to 4 alkyl group substituted by a halogen atom, (5) a C1 to 4 alkyl group substituted by a hydroxyl group, ( 6) C3 to 6 cycloalkyl, (7) C1 to 4 alkoxy, (8) carboxyl, (9)-CO 2 (C1 to 4 alkyl), (10) ethyl decyl amide, (11) a phosphinyloxy group and a (12) sulfonylamino group, R 7 is a C1 to 6 alkyl group, X is a bond or an oxygen atom, pa is an integer from 0 to 2, pb is an integer from 0 to 2, q is An integer from 0 to 2, ra is an integer from 0 to 1, and t is a compound represented by an integer from 0 to 2, a salt thereof, an N-oxide thereof, a solvate thereof, or such a precursor.

通式(I)表示之化合物中，通式(I-2-a)表示之化合物或通式(I-2-b)表示之化合物最好為(1)1-[5，6’-雙(三氟甲基)-2，3’-二吡啶-3-基]-3-(2-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(2)1-[2-(3，4-二甲基苯基)-5-(三氟甲基)-3-吡啶基]-3-(2-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(3)1-[2-(3，4-二甲基苯基)-5-(三氟甲基)-3-吡啶基]-3-(2-{4-[2-(異丙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(4)1-(2-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-(4-甲基苯基)-5-(三氟甲基)-3-吡啶基]脲、(5)1-(2-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-苯基 -5-(三氟甲基)-3-吡啶基]脲、(6)1-(2-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-(3-甲基苯基)-5-(三氟甲基)-3-吡啶基]脲、(7)1-[2-(3，4-二甲基苯基)-5-(三氟甲基)-3-吡啶基]-3-[2-(4-{2-[(2-甲基-2-丙基)胺基]-1，3-噻唑-5-基}苯氧基)-5-嘧啶基]脲、(8)1-[2-(3，4-二甲基苯基)-5-(三氟甲基)-3-吡啶基]-3-(6-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)脲、(9)1-(6-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)-3-[2-苯基-5-(三氟甲基)-3-吡啶基]脲、(10)1-(2-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}5-嘧啶基)-3-{2-[3-(羥基甲基)苯基]-5-(三氟甲基)-3-吡啶基}脲、(11)1-(2-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[5-(三氟甲基)-2，3’-二吡啶-3-基]脲、(12)1-[2-(3，4-二甲基苯基)-5-(三氟甲基)-3-吡啶基]-3-[2-(4-{2-[(2-乙氧基乙基)胺基]-1，3-噻唑-5-基}苯氧基)-5-嘧啶基]脲、(13)1-[2-(3，4-二甲基苯基)-5-(三氟甲基)-3-吡啶基]-3-(2-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(14)1-(2-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-(2-甲基苯基)-5-(三氟甲基)-3-吡啶基]脲、(15)1-(2-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-苯氧基-5-(三氟甲基)-3-吡啶基]脲、(16)1-(2-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-(6-甲基-3-吡啶基)-5-(三氟甲基)苯基]脲、(17)1-[2-(3，4-二甲基苯基)-5-甲基-3-吡啶基]-3-(2-{4-[2-(乙胺 基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(18)1-[2-(3，4-二甲基苯基)-3-吡啶基]-3-(2-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(19)1-(2-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-(3-吡啶基)-5-(三氟甲基)苯基]脲、(20)1-(2-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-(1H-咪唑-1-基)-5-(三氟甲基)苯基]脲、(21)1-(2-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-(3-吡啶基)-5-(三氟甲基)苯基]脲、(22)1-(6-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)-3-[2-(3-吡啶基)-5-(三氟甲基)苯基]脲、(23)1-(2-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-(1H-吡唑-1-基)-5-(三氟甲基)苯基]脲、(24)1-(2-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-{5-(三氟甲基)-2-[3-(三氟甲基)-1H-吡唑-1-基]苯基}脲、(25)1-[2-(1-甲基-1H-吡唑-5-基)-5-(三氟甲基)苯基]-3-(2-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(26)1-[2-(3-甲基-1H-吡唑-1-基)-5-(三氟甲基)苯基]-3-(2-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(27)1-[2-(4-甲基-1H-吡唑-1-基)-5-(三氟甲基)苯基]-3-(2-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(28)1-[2-(4-甲基-1H-1，2，3-三唑-1-基)-5-(三氟甲基)苯基]-3-(2-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(29)1-(2-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2- (1H-吡唑-1-基)-4-(三氟甲基)苯基]脲、(30)1-(2-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-(3-吡啶基)-4-(三氟甲基)苯基]脲、(31)1-[5-氯-2-(1H-吡唑-1-基)苯基]-3-(2-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(32)1-[5-氯-2-(3-吡啶基)苯基]-3-(2-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(33)1-(6-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)-3-[2-(1H-吡唑-1-基)-5-(三氟甲基)苯基]脲、(34)1-(6-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)-3-{5-(三氟甲基)-2-[3-(三氟甲基)-1H-吡唑-1-基]苯基}脲、(35)1-[2-(1-甲基-1H-吡唑-5-基)-5-(三氟甲基)苯基]-3-(6-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)脲、(36)1-[2-(3-甲基-1H-吡唑-1-基)-5-(三氟甲基)苯基]-3-(6-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)脲、(37)1-[2-(4-甲基-1H-吡唑-1-基)-5-(三氟甲基)苯基]-3-(6-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)脲、(38)1-(6-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)-3-[2-(1H-吡唑-1-基)-4-(三氟甲基)苯基]脲、(39)1-(6-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)-3-[2-(3-吡啶基)-4-(三氟甲基)苯基]脲、(40)1-[5-氯-2-(1H-吡唑-1-基)苯基]-3-(6-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)脲、(41)1-[5-氯-2-(3-吡啶基)苯基]-3-(6-{4-[2-(丙胺基)-1，3-噻唑-5-基] 苯氧基}-3-吡啶基)脲、(42)1-(2-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-(2H-1，2，3-三唑-2-基)-5-(三氟甲基)苯基]脲、(43)1-[5-氯-2-(1H-1，2，3-三唑-1-基)苯基]-3-(2-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(44)1-[5-氯-2-(2H-1，2，3-三唑-2-基)苯基]-3-(2-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(45)1-(6-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)-3-[2-(2H-1，2，3-三唑-2-基)-5-(三氟甲基)苯基]脲、(46)1-[5-氯-2-(1H-1，2，3-三唑-1-基)苯基]-3-(6-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)脲、(47)1-[5-氯-2-(2H-1，2，3-三唑-2-基)苯基]-3-(6-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)脲、(48)1-[2-(3-吡啶基)-5-(三氟甲基)苯基]-3-[2-(4-{2-[(四氫-2H-吡喃-4-基甲基)胺基]-1，3-噻唑-5-基}苯氧基)-5-嘧啶基]脲、或(49)1-{2-[3-(二氟甲基)-1H-吡唑-1-基]-5-(三氟甲基)苯基}-3-(2-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、其鹽、其N-氧化物、其溶劑化物或該等之前驅藥。 Among the compounds represented by the formula (I), the compound represented by the formula (I-2-a) or the compound represented by the formula (I-2-b) is preferably (1) 1-[5,6'-double (trifluoromethyl)-2,3'-dipyridin-3-yl]-3-(2-{4-[2-(ethylamino)-1,3-thiazol-5-yl]phenoxy }-5-pyrimidinyl)urea, (2) 1-[2-(3,4-dimethylphenyl)-5-(trifluoromethyl)-3-pyridyl]-3-(2-{ 4-[2-(ethylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (3) 1-[2-(3,4-dimethylbenzene 5-(3-trifluoromethyl)-3-pyridyl]-3-(2-{4-[2-(isopropylamino)-1,3-thiazol-5-yl]phenoxy}- 5-pyrimidinyl)urea, (4) 1-(2-{4-[2-(ethylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3- [2-(4-methylphenyl)-5-(trifluoromethyl)-3-pyridyl]urea, (5) 1-(2-{4-[2-(ethylamino)-1, 3-thiazol-5-yl]phenoxy}-5-pyrimidinyl-3-[2-phenyl -5-(Trifluoromethyl)-3-pyridyl]urea, (6) 1-(2-{4-[2-(ethylamino)-1,3-thiazol-5-yl]phenoxy }-5-pyrimidinyl-3-[2-(3-methylphenyl)-5-(trifluoromethyl)-3-pyridyl]urea, (7) 1-[2-(3,4 -Dimethylphenyl)-5-(trifluoromethyl)-3-pyridyl]-3-[2-(4-{2-[(2-methyl-2-propyl)amino]- 1,3-thiazol-5-yl}phenoxy)-5-pyrimidinyl]urea, (8) 1-[2-(3,4-dimethylphenyl)-5-(trifluoromethyl) -3-pyridyl]-3-(6-{4-[2-(ethylamino)-1,3-thiazol-5-yl]phenoxy}-3-pyridyl)urea, (9)1 -(6-{4-[2-(ethylamino)-1,3-thiazol-5-yl]phenoxy}-3-pyridyl)-3-[2-phenyl-5-(trifluoro Methyl)-3-pyridyl]urea, (10) 1-(2-{4-[2-(ethylamino)-1,3-thiazol-5-yl]phenoxy}5-pyrimidinyl) -3-{2-[3-(hydroxymethyl)phenyl]-5-(trifluoromethyl)-3-pyridyl}urea, (11) 1-(2-{4-[2-(B Amino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl-3-[5-(trifluoromethyl)-2,3'-dipyridin-3-yl]urea , (12) 1-[2-(3,4-dimethylphenyl)-5-(trifluoromethyl)-3-pyridyl]-3-[2-(4-{2-[(2) -ethoxyethyl)amino]-1,3-thiazol-5-yl}phenoxy)-5-pyrimidinyl]urea, (13) 1-[2-(3,4-dimethylbenzene Base)-5- (trifluoromethyl)-3-pyridyl]-3-(2-{4-[2-(propylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea , (14) 1-(2-{4-[2-(ethylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-[2-(2- Methylphenyl)-5-(trifluoromethyl)-3-pyridyl]urea, (15) 1-(2-{4-[2-(ethylamino)-1,3-thiazole-5- (phenoxy}-5-pyrimidinyl)-3-[2-phenoxy-5-(trifluoromethyl)-3-pyridyl]urea, (16) 1-(2-{4-[ 2-(ethylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl-3-[2-(6-methyl-3-pyridyl)-5-(three Fluoromethyl)phenyl]urea, (17) 1-[2-(3,4-dimethylphenyl)-5-methyl-3-pyridyl]-3-(2-{4-[2 -(ethylamine -1,3-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (18) 1-[2-(3,4-dimethylphenyl)-3-pyridinyl] -3-(2-{4-[2-(ethylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (19) 1-(2-{4 -[2-(ethylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-[2-(3-pyridyl)-5-(trifluoromethyl Phenyl]urea, (20) 1-(2-{4-[2-(ethylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-[ 2-(1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl]urea, (21) 1-(2-{4-[2-(propylamino)-1,3-thiazole- 5-yl]phenoxy}-5-pyrimidinyl-3-[2-(3-pyridyl)-5-(trifluoromethyl)phenyl]urea, (22) 1-(6-{4 -[2-(propylamino)-1,3-thiazol-5-yl]phenoxy}-3-pyridyl)-3-[2-(3-pyridyl)-5-(trifluoromethyl) Phenyl]urea, (23) 1-(2-{4-[2-(propylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-[2- (1H-pyrazol-1-yl)-5-(trifluoromethyl)phenyl]urea, (24) 1-(2-{4-[2-(propylamino)-1,3-thiazole-5 -yl]phenoxy}-5-pyrimidinyl)-3-{5-(trifluoromethyl)-2-[3-(trifluoromethyl)-1H-pyrazol-1-yl]phenyl} Urea, (25) 1-[2-(1-methyl-1H-pyrazol-5-yl)-5-(trifluoromethyl)phenyl]-3-(2-{4-[2-( Alanine)-1,3-thiazide -5-yl]phenoxy}-5-pyrimidinyl)urea, (26) 1-[2-(3-methyl-1H-pyrazol-1-yl)-5-(trifluoromethyl)benzene 3-(2-{4-[2-(propylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (27)1-[2-( 4-methyl-1H-pyrazol-1-yl)-5-(trifluoromethyl)phenyl]-3-(2-{4-[2-(propylamino)-1,3-thiazole-5 -yl]phenoxy}-5-pyrimidinyl)urea, (28) 1-[2-(4-methyl-1H-1,2,3-triazol-1-yl)-5-(trifluoro Methyl)phenyl]-3-(2-{4-[2-(propylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (29) 1- (2-{4-[2-(propylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-[2- (1H-pyrazol-1-yl)-4-(trifluoromethyl)phenyl]urea, (30) 1-(2-{4-[2-(propylamino)-1,3-thiazole-5 -yl]phenoxy}-5-pyrimidinyl-3-[2-(3-pyridyl)-4-(trifluoromethyl)phenyl]urea, (31) 1-[5-chloro-2 -(1H-pyrazol-1-yl)phenyl]-3-(2-{4-[2-(propylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl Urea, (32) 1-[5-chloro-2-(3-pyridyl)phenyl]-3-(2-{4-[2-(propylamino)-1,3-thiazol-5-yl) Phenoxy}-5-pyrimidinyl)urea, (33) 1-(6-{4-[2-(propylamino)-1,3-thiazol-5-yl]phenoxy}-3-pyridine 3-[2-(1H-pyrazol-1-yl)-5-(trifluoromethyl)phenyl]urea, (34) 1-(6-{4-[2-(propylamino) -1,3-thiazol-5-yl]phenoxy}-3-pyridyl)-3-{5-(trifluoromethyl)-2-[3-(trifluoromethyl)-1H-pyrazole -1-yl]phenyl}urea, (35) 1-[2-(1-methyl-1H-pyrazol-5-yl)-5-(trifluoromethyl)phenyl]-3-(6 -{4-[2-(propylamino)-1,3-thiazol-5-yl]phenoxy}-3-pyridyl)urea, (36) 1-[2-(3-methyl-1H- Pyrazol-1-yl)-5-(trifluoromethyl)phenyl]-3-(6-{4-[2-(propylamino)-1,3-thiazol-5-yl]phenoxy} -3-pyridyl)urea, (37) 1-[2-(4-methyl-1H-pyrazol-1-yl)-5-(trifluoromethyl)phenyl]-3-(6-{ 4-[2-(propylamino)-1,3-thiazide -5-yl]phenoxy}-3-pyridyl)urea, (38) 1-(6-{4-[2-(propylamino)-1,3-thiazol-5-yl]phenoxy} -3-pyridyl)-3-[2-(1H-pyrazol-1-yl)-4-(trifluoromethyl)phenyl]urea, (39) 1-(6-{4-[2- (propylamino)-1,3-thiazol-5-yl]phenoxy}-3-pyridyl)-3-[2-(3-pyridyl)-4-(trifluoromethyl)phenyl]urea , (40) 1-[5-Chloro-2-(1H-pyrazol-1-yl)phenyl]-3-(6-{4-[2-(propylamino)-1,3-thiazole-5 -yl]phenoxy}-3-pyridyl)urea, (41) 1-[5-chloro-2-(3-pyridyl)phenyl]-3-(6-{4-[2-(propylamine) Base)-1,3-thiazol-5-yl] Phenoxy}-3-pyridyl)urea, (42) 1-(2-{4-[2-(propylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl -3-[2-(2H-1,2,3-triazol-2-yl)-5-(trifluoromethyl)phenyl]urea, (43) 1-[5-chloro-2-( 1H-1,2,3-triazol-1-yl)phenyl]-3-(2-{4-[2-(propylamino)-1,3-thiazol-5-yl]phenoxy}- 5-pyrimidinyl)urea, (44) 1-[5-chloro-2-(2H-1,2,3-triazol-2-yl)phenyl]-3-(2-{4-[2- (propylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (45) 1-(6-{4-[2-(propylamino)-1,3- Thiazol-5-yl]phenoxy}-3-pyridyl)-3-[2-(2H-1,2,3-triazol-2-yl)-5-(trifluoromethyl)phenyl] Urea, (46) 1-[5-chloro-2-(1H-1,2,3-triazol-1-yl)phenyl]-3-(6-{4-[2-(propylamino)- 1,3-thiazol-5-yl]phenoxy}-3-pyridyl)urea, (47) 1-[5-chloro-2-(2H-1,2,3-triazol-2-yl) Phenyl]-3-(6-{4-[2-(propylamino)-1,3-thiazol-5-yl]phenoxy}-3-pyridyl)urea, (48)1-[2- (3-pyridyl)-5-(trifluoromethyl)phenyl]-3-[2-(4-{2-[(tetrahydro-2H-pyran-4-ylmethyl)amino]- 1,3-thiazol-5-yl}phenoxy)-5-pyrimidinyl]urea, or (49)1-{2-[3-(difluoromethyl)-1H-pyrazol-1-yl] -5-(trifluoromethyl)phenyl}-3-(2-{4 -[2-(Proamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, a salt thereof, an N-oxide thereof, a solvate thereof or such a prodrug.

通式(I)表示之化合物中，更好為下述通式(I-3-a)或通式(I-3-b)表示之化合物、其鹽、其N-氧化物、其溶劑化物或該等之前驅藥。 Among the compounds represented by the formula (I), a compound represented by the following formula (I-3-a) or formula (I-3-b), a salt thereof, an N-oxide thereof, and a solvate thereof are more preferred. Or such a previous drug.

[化26] [Chem. 26]

(式中，所有符號與上述[1]及[6]記載之符號同意義。) (In the formula, all symbols have the same meaning as the symbols described in [1] and [6] above.)

通式(I)表示之化合物中，通式(I-3-a)表示之化合物或通式(I-3-b)表示之化合物最好為下述通式(I-3-a-1)、通式(I-3-a-2)、通式(I-3-b-1)或通式(I-3-b-2)表示之化合物、其鹽、其N-氧化物、其溶劑化物或該等之前驅藥。 In the compound represented by the formula (I), the compound represented by the formula (I-3-a) or the compound represented by the formula (I-3-b) is preferably the following formula (I-3-a-1) a compound represented by the formula (I-3-a-2), the formula (I-3-b-1) or the formula (I-3-b-2), a salt thereof, an N-oxide thereof, Its solvate or such pre-drug.

(式中，ra表示0至3之整數，t表示0至4之整數，其他符號與上述[1]及[6]記載之符號同意義。) (wherein, ra represents an integer of 0 to 3, and t represents an integer of 0 to 4, and other symbols have the same meaning as the symbols described in the above [1] and [6].)

通式(I)表示之化合物中，通式(I-3-a-1)表示之化合物、通式(I-3-a-2)表示之化合物、通式(I-3-b-1)表示之化合物或通式(I-3-b-2)表示之化合物較好為該等通式之R1為(1)鹵素原子、(2)C1至4烷基、(3)經鹵素原子取代之C1至4烷基、(4)環丙基、(5)環丁基、(6)經鹵素原子取代之環丙基、(7)經鹵素原子取代之環丁基、(8)氧雜環丁烷基及(9)經甲基取代之氧雜環丁烷基，R2為異丙基、第二丁基、第三丁基、異丁基、氫原子、羥基、羧基、1-羥基-1-甲基乙基、2-羥基丙基、3-羥基-3-甲基-1-丁炔基、甲基磺醯基、甲基磺醯胺基及二甲基磺醯胺基，R3為氟原子、氯原子、甲基、三氟甲基及甲氧基，R4為氟原子、氯原子、甲基、三氟甲基及甲氧基，R7為C1至6烷基，pa為0至2之整數，pb為0至2之整數，ra為0至1之整數及t為0至2之整數表示之化合物、其鹽、其N-氧化物、其溶劑化物或該等之前驅藥，更好為該等通式之R1為鹵素原子、甲基、三氟甲基、第三丁基、1，1-二氟乙基、異丙基、環丙基、氧雜環丁烷基及二氟甲基，R2為異丙基、第二丁基、第三丁基、異丁基、氫原子、羥基、羧基、1-羥基-1-甲基乙基、2-羥基丙基、3-羥基-3-甲基-1-丁炔基、甲基磺醯基、甲基磺醯胺基及二甲基磺醯胺基，R3為氟原子、氯原子、甲基、三氟甲基及甲氧基，R4為氟原子、氯原子、甲基、三氟甲基及甲氧基，R7為C1至6烷基，pa為0至2之整數，pb為0至2之整數，ra為0至1之整數及t為0至2之整數表示之化合物、其鹽、其N-氧化物、其溶劑化物或該等之前驅藥，又更，好為該等通式之R1 為鹵素原子、甲基及三氟甲基，R2為異丙基、第二丁基、第三丁基、異丁基、氫原子、羥基、羧基、1-羥基-1-甲基乙基、2-羥基丙基、3-羥基-3-甲基-1-丁炔基、甲基磺醯基、甲基磺醯胺基及二甲基磺醯胺基，R3為氟原子、氯原子、甲基、三氟甲基及甲氧基，R4為氟原子、氯原子、甲基、三氟甲基及甲氧基，R7為C1至6烷基，pa為0至2之整數，pb為0至2之整數，ra為0至1之整數及t為0至2之整數表示之化合物、其鹽、其N-氧化物、其溶劑化物或該等之前驅藥。 In the compound represented by the formula (I), the compound represented by the formula (I-3-a-1), the compound represented by the formula (I-3-a-2), and the formula (I-3-b-1) The compound represented by the formula or the compound represented by the formula (I-3-b-2) is preferably such that R 1 is (1) a halogen atom, (2) a C1 to 4 alkyl group, and (3) a halogen. Atom-substituted C1 to 4 alkyl, (4) cyclopropyl, (5) cyclobutyl, (6) cyclopropyl substituted by halogen atom, (7) cyclobutyl substituted by halogen atom, (8) Oxetane and (9) methyl substituted oxetanyl, R 2 is isopropyl, t-butyl, tert-butyl, isobutyl, hydrogen, hydroxy, carboxy, 1-hydroxy-1-methylethyl, 2-hydroxypropyl, 3-hydroxy-3-methyl-1-butynyl, methylsulfonyl, methylsulfonylamino and dimethylsulfonate An amine group, R 3 is a fluorine atom, a chlorine atom, a methyl group, a trifluoromethyl group and a methoxy group, and R 4 is a fluorine atom, a chlorine atom, a methyl group, a trifluoromethyl group and a methoxy group, and R 7 is a C1 to 6 alkyl, pa is an integer of 0 to 2, pb is an integer of 0 to 2, ra is an integer of 0 to 1, and t is an integer represented by an integer of 0 to 2, a salt thereof, an N-oxide thereof, and a solvent thereof Compound or before R medicine, the better for such formula is a halogen atom, methyl, trifluoromethyl, tert-butyl, 1,1-difluoroethyl, isopropyl, cyclopropyl, oxetanyl Alkyl and difluoromethyl, R 2 is isopropyl, second butyl, tert-butyl, isobutyl, hydrogen, hydroxy, carboxy, 1-hydroxy-1-methylethyl, 2-hydroxy Propyl, 3-hydroxy-3-methyl-1-butynyl, methylsulfonyl, methylsulfonylamino and dimethylsulfonylamino, R 3 is a fluorine atom, a chlorine atom, a methyl group , trifluoromethyl and methoxy, R 4 is a fluorine atom, a chlorine atom, a methyl group, a trifluoromethyl group and a methoxy group, R 7 is a C1 to 6 alkyl group, pa is an integer of 0 to 2, and pb is An integer from 0 to 2, ra is an integer from 0 to 1, and t is a compound represented by an integer from 0 to 2, a salt thereof, an N-oxide thereof, a solvate thereof, or such a prodrug, and more preferably R 1 of the formula is a halogen atom, a methyl group and a trifluoromethyl group, and R 2 is an isopropyl group, a second butyl group, a tert-butyl group, an isobutyl group, a hydrogen atom, a hydroxyl group, a carboxyl group, a 1-hydroxy group- 1-methylethyl, 2-hydroxypropyl, 3-hydroxy-3-methyl-1-butynyl, methylsulfonyl, methylsulfonylamino Sulfonic dimethylamino group, R 3 is fluorine atom, chlorine atom, methyl, trifluoromethyl and methoxy, R 4 is a fluorine atom, chlorine atom, methyl, trifluoromethyl and methoxy, R 7 is a C1 to 6 alkyl group, pa is an integer of 0 to 2, pb is an integer of 0 to 2, ra is an integer of 0 to 1, and t is an integer represented by an integer of 0 to 2, a salt thereof, and N- An oxide, a solvate thereof or such a precursor.

通式(I)表示之化合物中，通式(I-3-a)表示之化合物或通式(I-3-b)表示之化合物最好為(1)1-(6-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-5-吡啶基)-3-[3-(三氟甲基)苯基]脲、(2)1-(2-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[3-(三氟甲基)苯基]脲、(3)1-(2-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-異丙基-5-(三氟甲基)-3-吡啶基]脲、(4)1-(2-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[4-甲基-3-(三氟甲基)苯基]脲、(5)1-(2-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[4-(三氟甲基)苯基]脲、(6)1-(2-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[3-氟-5-(三氟甲基)苯基]脲、(7)1-[2-氯-5-(三氟甲基)苯基]-3-(2-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、 (8)1-[2-氯-4-(三氟甲基)苯基]-3-(2-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(9)1-(2-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-氟-3-(三氟甲基)苯基]脲、(10)1-(2-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-氟-5-(三氟甲基)苯基]脲、(11)1-[2-(4-{2-[(3-羥基丙基)胺基]-1，3-噻唑-5-基}苯氧基)-5-嘧啶基]-3-[3-(三氟甲基)苯基]脲、(12)1-(2-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[3-(三氟甲基)苯基]脲、(13)1-[2-(4-{2-[(2-羥基乙基)胺基]-1，3-噻唑-5-基}苯氧基)-5-嘧啶基]-3-[3-(三氟甲基)苯基]脲、(14)1-(2-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[3-(三氟甲基)苯基]脲、(15)1-{2-[4-(2-{[2-(4-嗎啉基)乙基]胺基}-1，3-噻唑-5-基)苯氧基]-5-嘧啶基}-3-[3-(三氟甲基)苯基]脲、(16)1-[2-(4-{2-[(2-羥基丙基)胺基]-1，3-噻唑-5-基}苯氧基)-5-嘧啶基]-3-[3-(三氟甲基)苯基]脲、(17)1-[3-(二氟甲基)苯基]-3-(2-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(18)1-(3-乙醯基苯基)-3-(2-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(19)1-(2-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-(3-氟苯基)脲、 (20)1-[4-氯-3-(三氟甲基)苯基]-3-(2-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(21)1-(2-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-甲基-5-(三氟甲基)苯基]脲、(22)1-[3-氯-5-(三氟甲基)苯基]-3-(2-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(23)1-(2-{4-[2-(甲胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[3-(三氟甲基)苯基]脲、(24)1-(2-{4-[2-(異丙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[3-(三氟甲基)苯基]脲、(25)1-(2-{4-[2-(異丁胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[3-(三氟甲基)苯基]脲、(26)1-(3-氯苯基)-3-(2-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(27)1-(2，5-二氯苯基)-3-(2-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(28)1-[2-(4-{2-[(環丙基甲基)胺基]-1，3-噻唑-5-基}苯氧基)-5-嘧啶基]-3-[3-(三氟甲基)苯基]脲、(29)1-(2-{4-[2-(環丁胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[3-(三氟甲基)苯基]脲、(30)1-(2-{4-[2-(環戊胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[3-(三氟甲基)苯基]脲、(31)1-(6-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)-3-[2-氟-5-(三氟甲基)苯基]脲、 (32)1-[2-氯-5-(三氟甲基)苯基]-3-(6-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)脲、(33)1-[2-氯-4-(三氟甲基)苯基]-3-(6-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)脲、(34)1-(2-{4-[2-(四氫-3-呋喃基胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[3-(三氟甲基)苯基]脲、(35)1-(2-{4-[2-(3-氧雜環丁烷基胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[3-(三氟甲基)苯基]脲、(36)1-{2-[4-(2-{[2-(3-氧雜環丁烷基)乙基]胺基}-1，3-噻唑-5-基)苯氧基]-5-嘧啶基}-3-[3-(三氟甲基)苯基]脲、(37)1-[2-氯-5-(三氟甲基)苯基]-3-(2-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(38)1-[2-氯-4-(三氟甲基)苯基]-3-(2-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(39)1-[4-甲基-3-(三氟甲基)苯基]-3-(2-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(40)1-(6-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)-3-[3-(三氟甲基)苯基]脲、(41)1-(2-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[5-(三氟甲基)-3-吡啶基]脲、(42)1-[2-氯-5-(三氟甲基)-3-吡啶基]-3-(2-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(43)1-[2-(4-{2-[(2-甲氧基乙基)胺基]-1，3-噻唑-5-基}苯氧基)-5-嘧啶基]-3-[3-(三氟甲基)苯基]脲、 (44)1-(3，5-二氟苯基)-3-(2-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(45)1-[2-(4-{2-[(四氫-2H-吡喃-4-基甲基)胺基]-1，3-噻唑-5-基}苯氧基)-5-嘧啶基]-3-[3-(三氟甲基)苯基]脲、(46)1-[6-(4-{2-[(2-甲氧基乙基)胺基]-1，3-噻唑-5-基}苯氧基)-3-吡啶基]-3-[3-(三氟甲基)苯基]脲、(47)1-[2-氟-5-(三氟甲基)苯基]-3-(2-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(48)1-[2-甲基-5-(三氟甲基)苯基]-3-(2-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(49)1-(2，5-二氯苯基)-3-(2-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(50)1-(2，4-二氯苯基)-3-(2-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(51)1-(2，5-二氟苯基)-3-(2-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(52)1-[3-(二氟甲基)苯基]-3-(2-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(53)1-[2-氯-5-(三氟甲基)苯基]-3-(6-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)脲、(54)1-[2-氟-5-(三氟甲基)苯基]-3-(6-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)脲、(55)1-[2-甲基-5-(三氟甲基)苯基]-3-(6-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)脲、 (56)1-(2，5-二氯苯基)-3-(6-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)脲、(57)1-(2，4-二氯苯基)-3-(6-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)脲、(58)1-(2，5-二氟苯基)-3-(6-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)脲、(59)1-[3-(二氟甲基)苯基]-3-(6-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)脲、(60)1-[2-氯-4-(三氟甲基)苯基]-3-(6-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)脲、(61)1-(3，5-二氟苯基)-3-(2-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(62)N，N-二甲基-2-{[(2-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)胺基甲醯基]胺基}-4-(三氟甲基)苯磺醯胺、或(63)1-[2-(甲基磺醯基)-5-(三氟甲基)苯基]-3-(2-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、其鹽、其N-氧化物、其溶劑化物或該等之前驅藥。 In the compound represented by the formula (I), the compound represented by the formula (I-3-a) or the compound represented by the formula (I-3-b) is preferably (1) 1-(6-{4-[ 2-(ethylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyridyl)-3-[3-(trifluoromethyl)phenyl]urea, (2) 1- (2-{4-[2-(ethylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-[3-(trifluoromethyl)phenyl] Urea, (3) 1-(2-{4-[2-(ethylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-[2-isopropyl 5-(3-trifluoromethyl)-3-pyridyl]urea, (4) 1-(2-{4-[2-(ethylamino)-1,3-thiazol-5-yl]phenoxy 5-(4-pyrimidinyl)-3-[4-methyl-3-(trifluoromethyl)phenyl]urea, (5) 1-(2-{4-[2-(ethylamino)- 1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl-3-[4-(trifluoromethyl)phenyl]urea, (6) 1-(2-{4-[2 -(ethylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-[3-fluoro-5-(trifluoromethyl)phenyl]urea, (7 1-[2-chloro-5-(trifluoromethyl)phenyl]-3-(2-{4-[2-(ethylamino)-1,3-thiazol-5-yl]phenoxy }-5-pyrimidinyl)urea, (8) 1-[2-Chloro-4-(trifluoromethyl)phenyl]-3-(2-{4-[2-(ethylamino)-1,3-thiazol-5-yl]benzene Oxy}-5-pyrimidinyl)urea, (9) 1-(2-{4-[2-(ethylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl -3-[2-fluoro-3-(trifluoromethyl)phenyl]urea, (10) 1-(2-{4-[2-(ethylamino)-1,3-thiazole-5- (phenoxy}-5-pyrimidinyl)-3-[2-fluoro-5-(trifluoromethyl)phenyl]urea, (11) 1-[2-(4-{2-[(3) -hydroxypropyl)amino]-1,3-thiazol-5-yl}phenoxy)-5-pyrimidinyl]-3-[3-(trifluoromethyl)phenyl]urea, (12)1 -(2-{4-[2-(propylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl-3-[3-(trifluoromethyl)phenyl] Urea, (13) 1-[2-(4-{2-[(2-hydroxyethyl)amino]-1,3-thiazol-5-yl}phenoxy)-5-pyrimidinyl]-3 -[3-(Trifluoromethyl)phenyl]urea, (14) 1-(2-{4-[2-(propylamino)-1,3-thiazol-5-yl]phenoxy}-5 -pyrimidinyl-3-[3-(trifluoromethyl)phenyl]urea, (15) 1-{2-[4-(2-{[2-(4-morpholinyl)ethyl]amine }}-1,3-thiazol-5-yl)phenoxy]-5-pyrimidinyl}-3-[3-(trifluoromethyl)phenyl]urea, (16) 1-[2-(4 -{2-[(2-hydroxypropyl)amino]-1,3-thiazol-5-yl}phenoxy)-5-pyrimidinyl]-3-[3-(trifluoromethyl)phenyl Urea, (17) 1-[ 3-(Difluoromethyl)phenyl]-3-(2-{4-[2-(ethylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea (18) 1-(3-Ethylphenyl)-3-(2-{4-[2-(ethylamino)-1,3-thiazol-5-yl]phenoxy}-5- Pyrimidinyl)urea, (19) 1-(2-{4-[2-(ethylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-(3 -fluorophenyl)urea, (20) 1-[4-Chloro-3-(trifluoromethyl)phenyl]-3-(2-{4-[2-(ethylamino)-1,3-thiazol-5-yl]benzene Oxy}-5-pyrimidinyl)urea, (21) 1-(2-{4-[2-(ethylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl -3-[2-methyl-5-(trifluoromethyl)phenyl]urea, (22) 1-[3-chloro-5-(trifluoromethyl)phenyl]-3-(2- {4-[2-(ethylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (23) 1-(2-{4-[2-(A) Amino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl-3-[3-(trifluoromethyl)phenyl]urea, (24) 1-(2-{ 4-[2-(Isopropylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-[3-(trifluoromethyl)phenyl]urea, (25 1-(2-{4-[2-(isobutylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-[3-(trifluoromethyl) Phenyl]urea, (26) 1-(3-chlorophenyl)-3-(2-{4-[2-(ethylamino)-1,3-thiazol-5-yl]phenoxy} -5-pyrimidinyl)urea, (27) 1-(2,5-dichlorophenyl)-3-(2-{4-[2-(ethylamino)-1,3-thiazol-5-yl Phenoxy}-5-pyrimidinyl)urea, (28) 1-[2-(4-{2-[(cyclopropylmethyl)amino]-1,3-thiazol-5-yl}benzene Oxy)-5-pyrimidinyl]-3-[3-(trifluoromethyl)phenyl]urea, (29) 1-(2-{4-[2-(cyclobutylamino)-1,3 -thiazol-5-yl]phenoxy }-5-pyrimidinyl)-3-[3-(trifluoromethyl)phenyl]urea, (30) 1-(2-{4-[2-(cyclopentylamino)-1,3-thiazole -5-yl]phenoxy}-5-pyrimidinyl)-3-[3-(trifluoromethyl)phenyl]urea, (31) 1-(6-{4-[2-(ethylamino) )-1,3-thiazol-5-yl]phenoxy}-3-pyridyl)-3-[2-fluoro-5-(trifluoromethyl)phenyl]urea, (32) 1-[2-Chloro-5-(trifluoromethyl)phenyl]-3-(6-{4-[2-(ethylamino)-1,3-thiazol-5-yl]benzene Oxy}-3-pyridyl)urea, (33) 1-[2-chloro-4-(trifluoromethyl)phenyl]-3-(6-{4-[2-(ethylamino)- 1,3-thiazol-5-yl]phenoxy}-3-pyridyl)urea, (34) 1-(2-{4-[2-(tetrahydro-3-furanylamino)-1, 3-thiazol-5-yl]phenoxy}-5-pyrimidinyl-3-[3-(trifluoromethyl)phenyl]urea, (35) 1-(2-{4-[2-( 3-oxetanylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-[3-(trifluoromethyl)phenyl]urea, 36) 1-{2-[4-(2-{[2-(3-oxetanyl)ethyl]amino}-1,3-thiazol-5-yl)phenoxy]-5 -pyrimidinyl}-3-[3-(trifluoromethyl)phenyl]urea, (37) 1-[2-chloro-5-(trifluoromethyl)phenyl]-3-(2-{4 -[2-(propylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (38) 1-[2-chloro-4-(trifluoromethyl)benzene 3-(2-{4-[2-(propylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (39) 1-[4- 3-(trifluoromethyl)phenyl]-3-(2-{4-[2-(propylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl) Urea, (40) 1-(6-{4-[2-(propylamino)-1,3-thiazol-5-yl]phenoxy}-3-pyridyl)-3-[3-(trifluoro methyl) Urea, (41) 1-(2-{4-[2-(ethylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-[5- (Trifluoromethyl)-3-pyridyl]urea, (42) 1-[2-chloro-5-(trifluoromethyl)-3-pyridyl]-3-(2-{4-[2- (ethylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (43) 1-[2-(4-{2-[(2-methoxy B) Amino]-1,3-1,3-thiazol-5-yl}phenoxy)-5-pyrimidinyl]-3-[3-(trifluoromethyl)phenyl]urea, (44) 1-(3,5-Difluorophenyl)-3-(2-{4-[2-(ethylamino)-1,3-thiazol-5-yl]phenoxy}-5- Pyrimidinyl)urea, (45) 1-[2-(4-{2-[(tetrahydro-2H-pyran-4-ylmethyl)amino]-1,3-thiazol-5-yl}benzene Oxy)-5-pyrimidinyl]-3-[3-(trifluoromethyl)phenyl]urea, (46) 1-[6-(4-{2-[(2-methoxyethyl)) Amino]-1,3-1,3-thiazol-5-yl}phenoxy)-3-pyridyl]-3-[3-(trifluoromethyl)phenyl]urea, (47) 1-[2-fluoro -5-(Trifluoromethyl)phenyl]-3-(2-{4-[2-(propylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea , (48) 1-[2-Methyl-5-(trifluoromethyl)phenyl]-3-(2-{4-[2-(propylamino)-1,3-thiazol-5-yl] Phenoxy}-5-pyrimidinyl)urea, (49) 1-(2,5-dichlorophenyl)-3-(2-{4-[2-(propylamino)-1,3-thiazole- 5-yl]phenoxy}-5-pyrimidinyl)urea, (50) 1-(2,4-dichlorophenyl)-3-(2-{4-[2-(propylamino)-1, 3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (51) 1-(2,5-difluorophenyl)-3-(2-{4-[2-(propylamino) )-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (52) 1-[3-(difluoromethyl)phenyl]-3-(2-{4- [2-(propylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (53) 1-[2-chloro-5-(trifluoromethyl)phenyl ]-3-( 6-{4-[2-(propylamino)-1,3-thiazol-5-yl]phenoxy}-3-pyridyl)urea, (54) 1-[2-fluoro-5-(trifluoro Methyl)phenyl]-3-(6-{4-[2-(propylamino)-1,3-thiazol-5-yl]phenoxy}-3-pyridyl)urea, (55)1- [2-Methyl-5-(trifluoromethyl)phenyl]-3-(6-{4-[2-(propylamino)-1,3-thiazol-5-yl]phenoxy}-3 -pyridyl)urea, (56) 1-(2,5-Dichlorophenyl)-3-(6-{4-[2-(propylamino)-1,3-thiazol-5-yl]phenoxy}-3-pyridine Urea, (57) 1-(2,4-dichlorophenyl)-3-(6-{4-[2-(propylamino)-1,3-thiazol-5-yl]phenoxy} -3-pyridyl)urea, (58) 1-(2,5-difluorophenyl)-3-(6-{4-[2-(propylamino)-1,3-thiazol-5-yl] Phenoxy}-3-pyridyl)urea, (59) 1-[3-(difluoromethyl)phenyl]-3-(6-{4-[2-(propylamino)-1,3- Thiazol-5-yl]phenoxy}-3-pyridyl)urea, (60) 1-[2-chloro-4-(trifluoromethyl)phenyl]-3-(6-{4-[2 -(propylamino)-1,3-thiazol-5-yl]phenoxy}-3-pyridyl)urea, (61) 1-(3,5-difluorophenyl)-3-(2-{ 4-[2-(propylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (62) N,N-dimethyl-2-{[(2- {4-[2-(Proamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinylaminomethylamino]amino}-4-(trifluoromethyl)benzene Sulfonamide, or (63) 1-[2-(methylsulfonyl)-5-(trifluoromethyl)phenyl]-3-(2-{4-[2-(propylamino)-1 , 3-thiazole-5-yl]phenoxy}-5-pyrimidinyl)urea, a salt thereof, an N-oxide thereof, a solvate thereof or such a prodrug.

通式(I)表示之化合物更好為下述通式(I-4-a)表示之化合物、其鹽、其N-氧化物、其溶劑化物或該等之前驅藥。 The compound represented by the formula (I) is more preferably a compound represented by the following formula (I-4-a), a salt thereof, an N-oxide thereof, a solvate thereof or the like.

(式中，所有符號與上述[1]記載之符號同意義)，更好為下述通式(I-4-a-1)或通式(I-4-a-2)表示之化合物、其鹽、其N-氧化物、其溶劑化物或該等之前驅藥。 (wherein all symbols have the same meaning as the symbols described in the above [1]), more preferably a compound represented by the following formula (I-4-a-1) or formula (I-4-a-2), a salt thereof, an N-oxide thereof, a solvate thereof, or such a prodrug.

(式中，ra表示0至3之整數，t表示0至4之整數，其他符號與上述[1]記載之符號同意義)，特，好為下述通式(I-4-a-1-i)、通式(I-4-a-1-ii)、通式(I-4-a-2-i)或通式(I-4-a-2-ii)表示之化合物、其鹽、其N-氧化物、其溶劑化物或該等之前驅藥。 (wherein, ra represents an integer of 0 to 3, t represents an integer of 0 to 4, and other symbols have the same meaning as the symbols described in the above [1]), and is preferably the following general formula (I-4-a-1) -i) a compound represented by the formula (I-4-a-1-ii), the formula (I-4-a-2-i) or the formula (I-4-a-2-ii), a salt, an N-oxide thereof, a solvate thereof, or such a prodrug.

(式中，ra表示0至3之整數、t表示0至4之整數，其他符號與上述[1]及[6]記載之符號同意義。) (wherein, ra represents an integer of 0 to 3, and t represents an integer of 0 to 4, and other symbols have the same meaning as the symbols described in the above [1] and [6].)

通式(I)表示之化合物中，通式(I-4-a-1-i)表示之化合物、通式(I-4-a-1-ii)表示之化合物、通式(I-4-a-2-i)表示之化合物或通式(I-4-a-2-ii)表示之化合物較好為該等通式之環Cy2為C3至10單環式碳環或5至10員單環式雜環或二環式雜環，R1為(1)鹵素原 子、(2)C1至4烷基、(3)經鹵素原子取代之C1至4烷基、(4)環丙基、(5)環丁基、(6)經鹵素原子取代之環丙基、(7)經鹵素原子取代之環丁基、(8)氧雜環丁烷基及(9)經甲基取代之氧雜環丁烷基，R3為氟原子、氯原子、甲基、三氟甲基及甲氧基，R4為氟原子、氯原子、甲基、三氟甲基及甲氧基，R5為羥基及羥基甲基，R6為(1)鹵素原子、(2)羥基、(3)C1至4烷基、(4)經鹵素原子取代之C1至4烷基、(5)經羥基取代之C1至4烷基、(6)C3至6環烷基、(7)C1至4烷氧基、(8)羧基、(9)-CO2(C1至4烷基)、(10)乙醯基醯胺基、(11)膦醯基氧基及(12)磺醯胺基，pa為0至2之整數，pb為0至2之整數，q為0至2之整數，ra為0至1之整數，t為0至2之整數，u為0至1之整數及w為2至4之整數表示之化合物、其鹽、其N-氧化物、其溶劑化物或該等之前驅藥，更好為該等通式之環Cy2為環丙烷、苯、環己烷、茚烷、四氫萘、吡喃、呋喃、噻吩、吡咯、異唑、唑、異噻唑、噻唑、吡唑、咪唑、三唑、吡啶、吡啶酮、嗒、嘧啶、吡、四氫吡喃、四氫噻喃、哌啶、嗎啉、硫代嗎啉、四氫吡啶、苯并二烷、哌、全氫茚、二氫苯并呋喃、二氫苯并噻吩、吲哚啉、苯并二茂、苯并硫醇、二氫苯并唑、二氫苯并噻唑、色滿、硫代色滿、四氫喹啉、二氫苯并二英、二氫苯并氧硫雜環己二烯、二氫苯并、吲哚、苯并呋喃、苯并噻吩、吲唑及四氫萘，R1為(1)鹵素原子、(2)C1至4烷基、(3)經鹵素原子取代之C1至4烷基、(4)環丙基、(5)環丁基、(6)經鹵素原子取代之環丙基、(7)經鹵素原子取代之環丁基、(8)氧雜環丁烷基及(9)經甲基取代之氧雜環丁烷基，R3為氟原子、氯原子、甲基、三氟甲基及甲氧基，R4為氟原子、氯原子、甲基、 三氟甲基及甲氧基，R5為羥基及羥基甲基，R6為(1)鹵素原子、(2)羥基、(3)C1至4烷基、(4)經鹵素原子取代之C1至4烷基、(5)經羥基取代之C1至4烷基、(6)C3至6環烷基、(7)C1至4烷氧基、(8)羧基、(9)-CO2(C1至4烷基)、(10)乙醯基醯胺基、(11)膦醯基氧基及(12)磺醯胺基，pa為0至2之整數，pb為0至2之整數，q為0至2之整數，ra為0至1之整數，t為0至2之整數，u為0至1之整數及w為2至4之整數表示之化合物、其鹽、其N-氧化物、其溶劑化物或該等之前驅藥，，又再更好為該等通式之環Cy2為苯、吡啶、吡唑、咪唑及三唑，R1為(1)鹵素原子、(2)C1-4烷基、(3)經鹵素原子取代之C1-4烷基、(4)環丙基、(5)環丁基、(6)經鹵素原子取代之環丙基、(7)經鹵素原子取代之環丁基、(8)氧雜環丁烷基及(9)經甲基取代之氧雜環丁烷基，R3為氟原子、氯原子、甲基、三氟甲基及甲氧基，R4為氟原子、氯原子、甲基、三氟甲基及甲氧基，R5為羥基及羥基甲基，R6為(1)鹵素原子、(2)羥基、(3)C1至4烷基、(4)經鹵素原子取代之C1至4烷基、(5)經羥基取代之C1至4烷基、(6)C3至6環烷基、(7)C1至4烷氧基、(8)羧基、(9)-CO2(C1至4烷基)、(10)乙醯基醯胺基、(11)膦醯基氧基及(12)磺醯胺基，pa為0至2之整數，pb為0至2之整數，q為0至2之整數，ra為0至1之整數，t為0至2之整數，u為0至1之整數及w為2至4之整數表示之化合物、其鹽、其N-氧化物、其溶劑化物或該等之前驅藥。 Among the compounds represented by the formula (I), the compound represented by the formula (I-4-a-1-i), the compound represented by the formula (I-4-a-1-ii), and the formula (I-4) The compound represented by -a-2-i) or the compound represented by the formula (I-4-a-2-ii) is preferably a ring of the formula: Cy 2 is a C3 to 10 monocyclic carbocyclic ring or 5 to a 10-membered monocyclic heterocyclic or bicyclic heterocyclic ring, and R 1 is (1) a halogen atom, (2) a C1 to 4 alkyl group, (3) a C1 to 4 alkyl group substituted by a halogen atom, and (4) a ring. a propyl group, a (5) cyclobutyl group, (6) a cyclopropyl group substituted with a halogen atom, (7) a cyclobutyl group substituted with a halogen atom, (8) an oxetane group, and (9) a methyl group a substituted oxetane group, R 3 is a fluorine atom, a chlorine atom, a methyl group, a trifluoromethyl group, and a methoxy group, and R 4 is a fluorine atom, a chlorine atom, a methyl group, a trifluoromethyl group, and a methoxy group. R 5 is a hydroxyl group and a hydroxymethyl group, and R 6 is (1) a halogen atom, (2) a hydroxyl group, (3) a C1 to 4 alkyl group, (4) a C1 to 4 alkyl group substituted by a halogen atom, (5) C1 to 4 alkyl group substituted by a hydroxyl group, (6) C3 to 6 cycloalkyl group, (7) C1 to 4 alkoxy group, (8) carboxyl group, (9)-CO 2 (C1 to 4 alkyl group), ( 10) acetamidoamine, (11) phosphinyloxy and (12) sulfonylamino, pa is 0 to 2 Number, pb is an integer from 0 to 2, q is an integer from 0 to 2, ra is an integer from 0 to 1, t is an integer from 0 to 2, u is an integer from 0 to 1 and w is an integer from 2 to 4. a compound, a salt thereof, an N-oxide thereof, a solvate thereof, or a precursor thereof, more preferably a ring of the formula Cy 2 is cyclopropane, benzene, cyclohexane, decane or tetrahydronaphthalene. Pyran, furan, thiophene, pyrrole, iso Azole, Oxazole, isothiazole, thiazole, pyrazole, imidazole, triazole, pyridine, pyridone, anthracene Pyrimidine, pyridyl , tetrahydropyran, tetrahydrothiopyran, piperidine, morpholine, thiomorpholine, tetrahydropyridine, benzodiazepine Alkane , all hydroquinone, dihydrobenzofuran, dihydrobenzothiophene, porphyrin, benzodiazepine Mao, benzo Mercaptan, dihydrobenzo Azole, dihydrobenzothiazole, chroman, thiochroman, tetrahydroquinoline, dihydrobenzo English, dihydrobenzothiazepine, dihydrobenzo , hydrazine, benzofuran, benzothiophene, oxazole and tetrahydronaphthalene, R 1 is (1) a halogen atom, (2) a C1 to 4 alkyl group, and (3) a C1 to 4 alkyl group substituted by a halogen atom. (4) cyclopropyl, (5) cyclobutyl, (6) a cyclopropyl group substituted with a halogen atom, (7) a cyclobutyl group substituted with a halogen atom, (8) oxetanyl group and 9) a methyl-substituted oxetane group, R 3 is a fluorine atom, a chlorine atom, a methyl group, a trifluoromethyl group and a methoxy group, and R 4 is a fluorine atom, a chlorine atom, a methyl group, a trifluoromethyl group And methoxy, R 5 is hydroxy and hydroxymethyl, and R 6 is (1) halogen atom, (2) hydroxy group, (3) C1 to 4 alkyl group, (4) C1 to 4 alkyl group substituted by halogen atom a group, (5) a C1 to 4 alkyl group substituted by a hydroxyl group, (6) a C3 to 6 cycloalkyl group, (7) a C1 to a 4 alkoxy group, a (8) carboxyl group, and (9)-CO 2 (C1 to 4) Alkyl), (10) ethoxylated decylamino, (11) phosphinyloxy and (12) sulfonylamino, pa is an integer from 0 to 2, pb is an integer from 0 to 2, q is 0 An integer up to 2, ra is an integer from 0 to 1, t is an integer from 0 to 2, u is an integer from 0 to 1, and w is a compound represented by an integer from 2 to 4, a salt thereof, an N-oxide thereof, Solvate or such pre-drug, Then better for such a ring of formula Cy 2 is benzene, pyridine, pyrazole, imidazole, and triazole, R 1 is (1) a halogen atom, (2) C1-4 alkyl, (3) substituted with a halogen atom C1-4 alkyl, (4) cyclopropyl, (5) cyclobutyl, (6) cyclopropyl substituted by halogen atom, (7) cyclobutyl substituted by halogen atom, (8) oxa a cyclobutane group and (9) a methyl-substituted oxetanyl group, R 3 is a fluorine atom, a chlorine atom, a methyl group, a trifluoromethyl group and a methoxy group, and R 4 is a fluorine atom or a chlorine atom. Methyl, trifluoromethyl and methoxy, R 5 is a hydroxyl group and a hydroxymethyl group, and R 6 is (1) a halogen atom, (2) a hydroxyl group, (3) a C1 to a 4 alkyl group, and (4) a halogen atom. Substituted C1 to 4 alkyl, (5) C1 to 4 alkyl substituted by hydroxy, (6) C3 to 6 cycloalkyl, (7) C1 to 4 alkoxy, (8) carboxyl, (9)- CO 2 (C1 to 4 alkyl), (10) ethoxylated decylamino, (11) phosphinyloxy and (12) sulfonylamino, pa is an integer from 0 to 2, and pb is from 0 to 2. An integer, q is an integer from 0 to 2, ra is an integer from 0 to 1, t is an integer from 0 to 2, u is an integer from 0 to 1, and w is an integer represented by an integer from 2 to 4, a salt thereof, N-oxide, its solvate or before medicine.

通式(I)表示之化合物中，通式(I-4-a-1)表示之化合物或通式(I-4-a-2)表示之化合物最好為(1)1-[2-(4-{2-[2-(2-羥基-2-丙基)-1-吡咯啶基]-1，3-噻唑-5-基}苯氧 基)-5-嘧啶基]-3-[2-苯基-5-(三氟甲基)-3-吡啶基]脲、(2)1-(2-{4-[2-(1-氮雜環丁烷基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-苯基-5-(三氟甲基)-3-吡啶基]脲、(3)1-(2-{4-[2-(1-氮雜環丁烷基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-(3-吡啶基)-5-(三氟甲基)苯基]脲、(4)1-(2-{4-[2-(1-氮雜環丁烷基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[5-苯基-2-(三氟甲基)-4-吡啶基]脲、(5)1-(2-{4-[2-(1-氮雜環丁烷基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-(1H-1，2，3-三唑-1-基)-5-(三氟甲基)苯基]脲、或(6)1-(2-{4-[2-(1-氮雜環丁烷基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-(1H-吡唑-1-基)-5-(三氟甲基)苯基]脲、其鹽、其N-氧化物、其溶劑化物或該等之前驅藥。 In the compound represented by the formula (I), the compound represented by the formula (I-4-a-1) or the compound represented by the formula (I-4-a-2) is preferably (1) 1-[2- (4-{2-[2-(2-hydroxy-2-propyl)-1-pyrrolidinyl]-1,3-thiazol-5-yl}phenoxy -5-pyrimidinyl]-3-[2-phenyl-5-(trifluoromethyl)-3-pyridyl]urea, (2) 1-(2-{4-[2-(1- Azetidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl-3-[2-phenyl-5-(trifluoromethyl)-3-pyridyl Urea, (3) 1-(2-{4-[2-(1-azetidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3 -[2-(3-pyridyl)-5-(trifluoromethyl)phenyl]urea, (4) 1-(2-{4-[2-(1-azetidinyl)-1 , 3-thiazole-5-yl]phenoxy}-5-pyrimidinyl)-3-[5-phenyl-2-(trifluoromethyl)-4-pyridyl]urea, (5) 1-( 2-{4-[2-(1-azetidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl-3-[2-(1H-1, 2,3-triazol-1-yl)-5-(trifluoromethyl)phenyl]urea, or (6) 1-(2-{4-[2-(1-azetidinyl) -1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-[2-(1H-pyrazol-1-yl)-5-(trifluoromethyl)phenyl]urea , a salt thereof, an N-oxide thereof, a solvate thereof, or such a prodrug.

通式(I)表示之化合物中，更好為下述通式(I-5-a)或通式(I-5-b)表示之化合物、其鹽、其N-氧化物、其溶劑化物或該等之前驅藥， Among the compounds represented by the formula (I), a compound represented by the following formula (I-5-a) or formula (I-5-b), a salt thereof, an N-oxide thereof, and a solvate thereof are more preferred. Or such a previous drug,

(式中，所有符號與上述[1]及[6]記載之符號同意義。)，更好為下述通式(I-5-a-1)、通式(I-5-a-2)、通式(I-5-b-1)或通式 (I-5-b-2)表示之化合物、其鹽、其N-氧化物、其溶劑化物或該等之前驅藥。 (In the formula, all symbols have the same meaning as the symbols described in the above [1] and [6].), more preferably, the following general formula (I-5-a-1), general formula (I-5-a-2) ), general formula (I-5-b-1) or general formula A compound represented by (I-5-b-2), a salt thereof, an N-oxide thereof, a solvate thereof or the like.

(式中，ra表示0至3之整數，t表示0至4之整數，其他符號與上述[1]及[6]記載之符號同意義。) (wherein, ra represents an integer of 0 to 3, and t represents an integer of 0 to 4, and other symbols have the same meaning as the symbols described in the above [1] and [6].)

通式(I)表示之化合物中，通式(I-5-a-1)表示之化合物、通式(I-5-a-2)表示之化合物、通式(I-5-b-1)表示之化合物或通式(I-5-b-2)表示之化合物較好為該等通式之R1為(1)鹵素原子、(2)C1至4烷基、(3)經鹵素原子取代之C1至4烷基、(4)環丙基、(5)環丁基、(6)經鹵素原子取代之環丙基、(7)經鹵素原子取代之環丁基、(8)氧雜環丁烷基及(9)經甲基取代之氧雜環丁烷基，R2為異丙基、第二丁基、第三丁基、異丁基、氫原子、羥基、羧基、1-羥基-1-甲基乙基、2-羥基丙基、3-羥基-3-甲基-1-丁炔基、甲基磺醯基、甲基磺醯胺基及二甲基磺醯胺基，R3為氟原子、氯原子、 甲基、三氟甲基及甲氧基，R4為氟原子、氯原子、甲基、三氟甲基及甲氧基，R5為鹵素原子、羥基或可經羥基取代之C1至4烷基，pa為0至2之整數，pb為0至2之整數，ra為0至1之整數，t為0至2之整數，u為0至1之整數及w為2至4之整數表示之化合物、其鹽、其N-氧化物、其溶劑化物或該等之前驅藥，更好為該等通式之R1為鹵素原子、甲基、三氟甲基、第三丁基、1，1-二氟乙基、異丙基、環丙基、氧雜環丁烷基及二氟甲基，R2為異丙基、第二丁基、第三丁基、異丁基、氫原子、羥基、羧基、1-羥基-1-甲基乙基、2-羥基丙基、3-羥基-3-甲基-1-丁炔基、甲基磺醯基、甲基磺醯胺基及二甲基磺醯胺基，R3為氟原子、氯原子、甲基、三氟甲基及甲氧基，R4為氟原子、氯原子、甲基、三氟甲基及甲氧基，R5為鹵素原子、羥基或可經羥基取代之C1至4烷基，pa為0至2之整數，pb為0至2之整數，ra為0至1之整數，t為0至2之整數，u為0至1之整數及w為2至4之整數表示之化合物、其鹽、其N-氧化物、其溶劑化物或該等之前驅藥，，又再更好為該等通式之R1為鹵素原子、甲基及三氟甲基，R2為異丙基、第二丁基、第三丁基、異丁基、氫原子、羥基、羧基、1-羥基-1-甲基乙基、2-羥基丙基、3-羥基-3-甲基-1-丁炔基、甲基磺醯基、甲基磺醯胺基及二甲基磺醯胺基，R3為氟原子、氯原子、甲基、三氟甲基及甲氧基，R4為氟原子、氯原子、甲基、三氟甲基及甲氧基，R5為鹵素原子、羥基或可經羥基取代之C1至4烷基，pa為0至2之整數，pb為0至2之整數，ra為0至1之整數，t為0至2之整數，u為0至1之整數及w為2至4之整數表示之化合物、其鹽、其N-氧化物、其溶劑化物或該等之前驅藥。 In the compound represented by the formula (I), the compound represented by the formula (I-5-a-1), the compound represented by the formula (I-5-a-2), and the formula (I-5-b-1) The compound represented by the formula or the compound represented by the formula (I-5-b-2) is preferably such that R 1 is (1) a halogen atom, (2) a C1 to 4 alkyl group, and (3) a halogen. Atom-substituted C1 to 4 alkyl, (4) cyclopropyl, (5) cyclobutyl, (6) cyclopropyl substituted by halogen atom, (7) cyclobutyl substituted by halogen atom, (8) Oxetane and (9) methyl substituted oxetanyl, R 2 is isopropyl, t-butyl, tert-butyl, isobutyl, hydrogen, hydroxy, carboxy, 1-hydroxy-1-methylethyl, 2-hydroxypropyl, 3-hydroxy-3-methyl-1-butynyl, methylsulfonyl, methylsulfonylamino and dimethylsulfonate An amine group, R 3 is a fluorine atom, a chlorine atom, a methyl group, a trifluoromethyl group and a methoxy group, R 4 is a fluorine atom, a chlorine atom, a methyl group, a trifluoromethyl group and a methoxy group, and R 5 is a halogen atom. a hydroxyl group or a C1 to 4 alkyl group which may be substituted by a hydroxyl group, pa is an integer of 0 to 2, pb is an integer of 0 to 2, ra is an integer of 0 to 1, t is an integer of 0 to 2, and u is 0 to An integer of 1 and w is 2 to 4 The compound represented by an integer, a salt thereof, an N-oxide thereof, a solvate thereof, or the like, preferably R 1 of the formula is a halogen atom, a methyl group, a trifluoromethyl group, a third group 1,1,1-difluoroethyl, isopropyl, cyclopropyl, oxetanyl and difluoromethyl, R 2 is isopropyl, second butyl, tert-butyl, isobutyl Base, hydrogen atom, hydroxyl group, carboxyl group, 1-hydroxy-1-methylethyl group, 2-hydroxypropyl group, 3-hydroxy-3-methyl-1-butynyl group, methylsulfonyl group, methylsulfonate Amidino and dimethylsulfonylamino, R 3 is a fluorine atom, a chlorine atom, a methyl group, a trifluoromethyl group and a methoxy group, and R 4 is a fluorine atom, a chlorine atom, a methyl group, a trifluoromethyl group and Methoxy, R 5 is a halogen atom, a hydroxyl group or a C1 to 4 alkyl group which may be substituted by a hydroxyl group, pa is an integer of 0 to 2, pb is an integer of 0 to 2, ra is an integer of 0 to 1, and t is 0. An integer of 2, wherein u is an integer from 0 to 1, and w is a compound represented by an integer from 2 to 4, a salt thereof, an N-oxide thereof, a solvate thereof, or the like, and further preferably R 1 of the formula is a halogen atom, a methyl group and a trifluoromethyl group, R 2 is an isopropyl group, and the second Butyl, tert-butyl, isobutyl, hydrogen, hydroxy, carboxy, 1-hydroxy-1-methylethyl, 2-hydroxypropyl, 3-hydroxy-3-methyl-1-butynyl , methylsulfonyl, methylsulfonylamino and dimethylsulfonylamino, R 3 is a fluorine atom, a chlorine atom, a methyl group, a trifluoromethyl group and a methoxy group, and R 4 is a fluorine atom or a chlorine atom. Atom, methyl, trifluoromethyl and methoxy, R 5 is a halogen atom, a hydroxyl group or a C1 to 4 alkyl group which may be substituted by a hydroxyl group, pa is an integer of 0 to 2, and pb is an integer of 0 to 2, ra An integer from 0 to 1, t is an integer from 0 to 2, u is an integer from 0 to 1, and w is a compound represented by an integer from 2 to 4, a salt thereof, an N-oxide thereof, a solvate thereof or the like Expelling medicine.

通式(I)表示之化合物中，通式(I-5-a)表示之化合物或通式(I-5-b)表示之化合物最好為(1)1-[2-(4-{2-[3-(羥基甲基)-1-吡咯啶基]-1，3-噻唑-5-基}苯氧基)-5-嘧啶基]-3-[3-(三氟甲基)苯基]脲、(2)1-(6-{4-[2-(1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)-3-[3-(三氟甲基)苯基]脲、(3)1-(6-{4-[2-(1-哌啶基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)-3-[3-(三氟甲基)苯基]脲、(4)1-(2-{4-[2-(1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[3-(三氟甲基)苯基]脲、(5)1-(2-{4-[2-(1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[3-(三氟甲基)苯基]脲、(6)1-(2-{4-[2-(1-氮雜環丁烷基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[3-(三氟甲基)苯基]脲、(7)1-(2-{4-[2-(3-羥基-1-氧雜環丁烷基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[3-(三氟甲基)苯基]脲、(8)1-(2-{4-[2-(1-氮雜環丁烷基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-(2，6-二氟苯基)脲、(9)1-(2-{4-[2-(1-氮雜環丁烷基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-(2，4-二氟苯基)脲、(10)1-(2-{4-[2-(1-氮雜環丁烷基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-(3，5-二氟苯基)脲、(11)1-(2-{4-[2-(1-氮雜環丁烷基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[3-氟-5-(三氟甲基)苯基]脲、 (12)1-(2-{4-[2-(1-氮雜環丁烷基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[4-甲基-3-(三氟甲基)苯基]脲、(13)1-(2-{4-[2-(1-氮雜環丁烷基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-氯-4-(三氟甲基)苯基]脲、(14)1-(2-{4-[2-(1-氮雜環丁烷基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-(2，5-二氟苯基)脲、(15)1-(2-{4-[2-(1-氮雜環丁烷基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-(3，4-二氟苯基)脲、(16)1-(2-{4-[2-(1-氮雜環丁烷基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-(2-氟苯基)脲、(17)1-(2-{4-[2-(3-羥基-3-甲基-1-氧雜環丁烷基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[3-(三氟甲基)苯基]脲、(18)1-(2-{4-[2-(3，3-二氟-1-氧雜環丁烷基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[3-(三氟甲基)苯基]脲、(19)1-(2-{4-[2-(1-氮雜環丁烷基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-(4-氟苯基)脲、(20)1-(2-{4-[2-(1-氮雜環丁烷基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[3-(二氟甲基)苯基]脲、(21)1-(2-{4-[2-(1-氮雜環丁烷基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-(2，3，5-三氟苯基)脲、(22)1-(2-{4-[2-(1-氮雜環丁烷基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-氯-5-(三氟甲基)苯基]脲、(23)1-(2-{4-[2-(1-氮雜環丁烷基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-(2，4，6-三氟苯基)脲、 (24)1-(2-{4-[2-(1-氮雜環丁烷基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-氟-5-(三氟甲基)苯基]脲、(25)1-(2-{4-[2-(1-氮雜環丁烷基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-(2，3-二氟苯基)脲、(26)1-(2-{4-[2-(1-氮雜環丁烷基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-(2，4，5-三氟苯基)脲、(27)1-(2-{4-[2-(1-氮雜環丁烷基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-(2，3，4-三氟苯基)脲、(28)1-(2-{4-[2-(1-氮雜環丁烷基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-(2，3，5，6-四氟苯基)脲、(29)1-(2-{4-[2-(1-氮雜環丁烷基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-甲基-5-(三氟甲基)苯基]脲或(30)1-(2-{4-[2-(1-氮雜環丁烷基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-(三氟甲基)-4-吡啶基]脲、其鹽、其N-氧化物、其溶劑化物或該等之前驅藥。 Among the compounds represented by the formula (I), the compound represented by the formula (I-5-a) or the compound represented by the formula (I-5-b) is preferably (1) 1-[2-(4-{ 2-[3-(Hydroxymethyl)-1-pyrrolidinyl]-1,3-thiazol-5-yl}phenoxy)-5-pyrimidinyl]-3-[3-(trifluoromethyl) Phenyl]urea, (2) 1-(6-{4-[2-(1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-3-pyridyl)-3- [3-(Trifluoromethyl)phenyl]urea, (3) 1-(6-{4-[2-(1-piperidinyl)-1,3-thiazol-5-yl]phenoxy} -3-pyridyl)-3-[3-(trifluoromethyl)phenyl]urea, (4) 1-(2-{4-[2-(1-pyrrolidinyl)-1,3-thiazole -5-yl]phenoxy}-5-pyrimidinyl)-3-[3-(trifluoromethyl)phenyl]urea, (5) 1-(2-{4-[2-(1-pipeper (pyridine)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-[3-(trifluoromethyl)phenyl]urea, (6) 1-(2-{ 4-[2-(1-azetidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl-3-[3-(trifluoromethyl)phenyl Urea, (7) 1-(2-{4-[2-(3-hydroxy-1-oxetanyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidine Benzyl-3-(3-(trifluoromethyl)phenyl]urea, (8) 1-(2-{4-[2-(1-azetidinyl)-1,3-thiazole- 5-yl]phenoxy}-5-pyrimidinyl)-3-(2,6-difluorophenyl)urea, (9) 1-(2-{4- [2-(1-azetidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-(2,4-difluorophenyl)urea, 10) 1-(2-{4-[2-(1-azetidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-(3, 5-difluorophenyl)urea, (11) 1-(2-{4-[2-(1-azetidinyl)-1,3-thiazol-5-yl]phenoxy}-5 -pyrimidinyl)-3-[3-fluoro-5-(trifluoromethyl)phenyl]urea, (12) 1-(2-{4-[2-(1-Azetidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-[4 -methyl-3-(trifluoromethyl)phenyl]urea, (13) 1-(2-{4-[2-(1-azetidinyl)-1,3-thiazole-5- (phenoxy}-5-pyrimidinyl)-3-[2-chloro-4-(trifluoromethyl)phenyl]urea, (14) 1-(2-{4-[2-(1- Azetidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-(2,5-difluorophenyl)urea, (15) 1-(2 -{4-[2-(1-azetidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-(3,4-difluorophenyl) Urea, (16) 1-(2-{4-[2-(1-azetidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3 -(2-fluorophenyl)urea, (17) 1-(2-{4-[2-(3-hydroxy-3-methyl-1-oxetanyl)-1,3-thiazole- 5-yl]phenoxy}-5-pyrimidinyl)-3-[3-(trifluoromethyl)phenyl]urea, (18) 1-(2-{4-[2-(3,3- Difluoro-1-oxetanyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl-3-[3-(trifluoromethyl)phenyl]urea, (19) 1-(2-{4-[2-(1-Azetidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-(4) -fluorophenyl)urea, (20) 1-(2-{4-[2-(1-azetidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidine base) -3-[3-(difluoromethyl)phenyl]urea, (21) 1-(2-{4-[2-(1-azetidinyl)-1,3-thiazole-5- (Phenoxy)-5-pyrimidinyl)-3-(2,3,5-trifluorophenyl)urea, (22) 1-(2-{4-[2-(1-azetidine) Alkyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-[2-chloro-5-(trifluoromethyl)phenyl]urea, (23) 1- (2-{4-[2-(1-azetidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-(2,4,6- Trifluorophenyl)urea, (24) 1-(2-{4-[2-(1-Azetidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-[2 -fluoro-5-(trifluoromethyl)phenyl]urea, (25) 1-(2-{4-[2-(1-azetidinyl)-1,3-thiazol-5-yl Phenoxy}-5-pyrimidinyl)-3-(2,3-difluorophenyl)urea, (26) 1-(2-{4-[2-(1-azetidinyl) -1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-(2,4,5-trifluorophenyl)urea, (27) 1-(2-{4-[ 2-(1-azetidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl-3-(2,3,4-trifluorophenyl)urea, (28) 1-(2-{4-[2-(1-Azetidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-(2) ,3,5,6-tetrafluorophenyl)urea, (29) 1-(2-{4-[2-(1-azetidinyl)-1,3-thiazol-5-yl]benzene Oxy}-5-pyrimidinyl-3-[2-methyl-5-(trifluoromethyl)phenyl]urea or (30) 1-(2-{4-[2-(1-aza) Cyclobutane)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-[2-(trifluoromethyl)-4-pyridyl]urea, a salt thereof, N-oxide, its solvate or such prodrugs.

通式(I)表示之化合物中，更好為下述通式(I-6-a)或通式(I-6-b)表示之化合物、其鹽、其N-氧化物、其溶劑化物或該等之前驅藥 Among the compounds represented by the formula (I), a compound represented by the following formula (I-6-a) or formula (I-6-b), a salt thereof, an N-oxide thereof, and a solvate thereof are more preferred. Or such pre-drugs

(式中，所有符號與上述[1]及[6]記載之符號同意義。)，更好為下述通式(I-6-a-1)、通式(I-6-a-2)、通式(I-6-b-1)或通式(I-6-b-2)表示之化合物、其鹽、其N-氧化物、其溶劑化物或該等之前驅藥。 (In the formula, all symbols have the same meaning as the symbols described in the above [1] and [6].), more preferably, the following general formula (I-6-a-1), general formula (I-6-a-2) a compound represented by the formula (I-6-b-1) or the formula (I-6-b-2), a salt thereof, an N-oxide thereof, a solvate thereof or the like.

(式中，ra表示0至3之整數，t表示0至4之整數，其 他符號與上述[1]及[6]記載之符號同意義。) (where ra represents an integer from 0 to 3, and t represents an integer from 0 to 4, His symbols have the same meaning as the symbols described in [1] and [6] above. )

通式(I)表示之化合物中，通式(I-6-a-1)表示之化合物、通式(I-6-a-2)表示之化合物、通式(I-6-b-1)表示之化合物或通式(I-6-b-2)表示之化合物較好為該等通式之R1為(1)鹵素原子、(2)C1至4烷基、(3)經鹵素原子取代之C1至4烷基、(4)環丙基、(5)環丁基、(6)經鹵素原子取代之環丙基、(7)經鹵素原子取代之環丁基、(8)氧雜環丁烷基及(9)經甲基取代之氧雜環丁烷基，R2為異丙基、第二丁基、第三丁基、異丁基、氫原子、羥基、羧基、1-羥基-1-甲基乙基、2-羥基丙基、3-羥基-3-甲基-1-丁炔基、甲基磺醯基、甲基磺醯胺基及二甲基磺醯胺基，R3為氟原子、氯原子、甲基、三氟甲基及甲氧基，R4為氟原子、氯原子、甲基、三氟甲基及甲氧基，R5為鹵素原子、羥基或可經羥基取代之C1至4烷基，pa為0至2之整數，pb為0至2之整數，ra為0至1之整數，t為0至2之整數，u為0至1之整數及w為2至4之整數表示之化合物、其鹽、其N-氧化物、其溶劑化物或該等之前驅藥，更好為該等通式之R1為鹵素原子、甲基、三氟甲基、第三丁基、1，1-二氟乙基、異丙基、環丙基、氧雜環丁烷基及二氟甲基，R2為異丙基、第二丁基、第三丁基、異丁基、氫原子、羥基、羧基、1-羥基-1-甲基乙基、2-羥基丙基、3-羥基-3-甲基-1-丁炔基、甲基磺醯基、甲基磺醯胺基及二甲基磺醯胺基，R3為氟原子、氯原子、甲基、三氟甲基及甲氧基，R4為氟原子、氯原子、甲基、三氟甲基及甲氧基，R5為鹵素原子、羥基或可經羥基取代之C1至4烷基，pa為0至2之整數，pb為0至2之整數，ra為0至1之整數，t為0至2之整數，u為0至1之整數及w為2至4之整數表示之 化合物、其鹽、其N-氧化物、其溶劑化物或該等之前驅藥，更好為該等通式之R1為鹵素原子、甲基及三氟甲基，R2為異丙基、第二丁基、第三丁基、異丁基、氫原子、羥基、羧基、1-羥基-1-甲基乙基、2-羥基丙基、3-羥基-3-甲基-1-丁炔基、甲基磺醯基、甲基磺醯胺基及二甲基磺醯胺基，R3為氟原子、氯原子、甲基、三氟甲基及甲氧基，R4為氟原子、氯原子、甲基、三氟甲基及甲氧基，R5為鹵素原子、羥基或可經羥基取代之C1至4烷基，pa為0至2之整數，pb為0至2之整數，ra為0至1之整數，t為0至2之整數，u為0至1之整數及w為2至4之整數表示之化合物、其鹽、其N-氧化物、其溶劑化物或該等之前驅藥。 Among the compounds represented by the formula (I), the compound represented by the formula (I-6-a-1), the compound represented by the formula (I-6-a-2), and the formula (I-6-b-1) The compound represented by the formula or the compound represented by the formula (I-6-b-2) is preferably such that R 1 of the formula is (1) a halogen atom, (2) a C1 to 4 alkyl group, and (3) a halogen. Atom-substituted C1 to 4 alkyl, (4) cyclopropyl, (5) cyclobutyl, (6) cyclopropyl substituted by halogen atom, (7) cyclobutyl substituted by halogen atom, (8) Oxetane and (9) methyl substituted oxetanyl, R 2 is isopropyl, t-butyl, tert-butyl, isobutyl, hydrogen, hydroxy, carboxy, 1-hydroxy-1-methylethyl, 2-hydroxypropyl, 3-hydroxy-3-methyl-1-butynyl, methylsulfonyl, methylsulfonylamino and dimethylsulfonate An amine group, R 3 is a fluorine atom, a chlorine atom, a methyl group, a trifluoromethyl group and a methoxy group, and R 4 is a fluorine atom, a chlorine atom, a methyl group, a trifluoromethyl group and a methoxy group, and R 5 is a halogen atom. a hydroxyl group or a C1 to 4 alkyl group which may be substituted by a hydroxyl group, pa is an integer of 0 to 2, pb is an integer of 0 to 2, ra is an integer of 0 to 1, t is an integer of 0 to 2, and u is 0 to An integer of 1 and w is 2 to 4 R represents an integer of compound, its salts, N- oxides thereof, solvates thereof or prodrugs of these, the better for such formula is a halogen atom, methyl, trifluoromethyl, tert-butyl 1,1-difluoroethyl, isopropyl, cyclopropyl, oxetanyl and difluoromethyl, R 2 is isopropyl, second butyl, tert-butyl, isobutyl , hydrogen atom, hydroxyl group, carboxyl group, 1-hydroxy-1-methylethyl group, 2-hydroxypropyl group, 3-hydroxy-3-methyl-1-butynyl group, methylsulfonyl group, methylsulfonate Amino group and dimethylsulfonylamino group, R 3 is a fluorine atom, a chlorine atom, a methyl group, a trifluoromethyl group and a methoxy group, and R 4 is a fluorine atom, a chlorine atom, a methyl group, a trifluoromethyl group and a group An oxy group, R 5 is a halogen atom, a hydroxyl group or a C1 to 4 alkyl group which may be substituted by a hydroxyl group, pa is an integer of 0 to 2, pb is an integer of 0 to 2, ra is an integer of 0 to 1, and t is 0 to An integer of 2, wherein u is an integer from 0 to 1, and w is a compound represented by an integer from 2 to 4, a salt thereof, an N-oxide thereof, a solvate thereof, or such a precursor, preferably more preferably R 1 is a halogen atom, and trifluoromethyl, R 2 is isopropyl, sec-butyl, Tributyl, isobutyl, hydrogen, hydroxy, carboxy, 1-hydroxy-1-methylethyl, 2-hydroxypropyl, 3-hydroxy-3-methyl-1-butynyl, methyl sulfonate Anthracenyl, methylsulfonylamino and dimethylsulfonylamino, R 3 is a fluorine atom, a chlorine atom, a methyl group, a trifluoromethyl group and a methoxy group, and R 4 is a fluorine atom, a chlorine atom or a methyl group. , trifluoromethyl and methoxy, R 5 is a halogen atom, a hydroxyl group or a C1 to 4 alkyl group which may be substituted by a hydroxyl group, pa is an integer of 0 to 2, pb is an integer of 0 to 2, and ra is 0 to 1. An integer, t is an integer from 0 to 2, u is an integer from 0 to 1, and w is a compound represented by an integer from 2 to 4, a salt thereof, an N-oxide thereof, a solvate thereof, or such a precursor.

通式(I)表示之化合物中，通式(I-6-a)表示之化合物或通式(I-6-b)表示之化合物更好為(1)1-[2-異丙基-5-(三氟甲基)-3-吡啶基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(2)1-[2-異丙基-5-(三氟甲基)-3-吡啶基]-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(3)1-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[3-(三氟甲基)苯基]脲、(4)1-[2-氯-5-(三氟甲基)-3-吡啶基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(5)1-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[5-(三氟甲基)-3-吡啶基]脲、(6)1-[3-羥基-5-(三氟甲基)苯基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、 (7)1-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[4-(三氟甲基)-2-吡啶基]脲、(8)2-{[(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)胺基甲醯基]胺基}-4-(三氟甲基)苯甲酸、(9)1-[2-(2-羥基-2-丙基)-5-(三氟甲基)苯基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(10)1-[3，5-雙(三氟甲基)苯基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(11)1-[2-(3-羥基-3-甲基-1-丁炔-1-基)-5-(三氟甲基)-3-吡啶基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(12)1-[2-(2-羥基-2-丙基)-5-(三氟甲基)-3-吡啶基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(13)1-[2-甲氧基-5-(三氟甲基)-3-吡啶基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(14)1-(2-{3-甲基-4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[3-(三氟甲基)苯基]脲、(15)1-[2-({6-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]-3-吡啶基}氧基)-5-嘧啶基]-3-[3-(三氟甲基)苯基]脲、(16)1-[2-(4-{2-[3-(2-羥基-2-丙基)-2-側氧基-1-吡咯啶基]-1，3-噻唑-5-基}苯氧基)-5-嘧啶基]-3-[3-(三氟甲基)苯基]脲、(17)1-[3-(二氟甲基)苯基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(18)1-[3-(1，1-二氟乙基)苯基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)- 1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、或(19)1-[2-(4-{2-[3-(2-羥基-2-丙基)-2-側氧基-1-吡咯啶基]-1，3-噻唑-5-基}苯氧基)-5-嘧啶基]-3-[2-(甲基磺醯基)-5-(三氟甲基)苯基]脲、其鹽、其N-氧化物、其溶劑化物或該等之前驅藥。 In the compound represented by the formula (I), the compound represented by the formula (I-6-a) or the compound represented by the formula (I-6-b) is more preferably (1) 1-[2-isopropyl- 5-(Trifluoromethyl)-3-pyridyl]-3-(2-{4-[2-(2-o-oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl] Phenoxy}-5-pyrimidinyl)urea, (2) 1-[2-isopropyl-5-(trifluoromethyl)-3-pyridyl]-3-(2-{4-[2- (2-Sideoxy-1-piperidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (3) 1-(2-{4-[2- (2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl-3-[3-(trifluoromethyl)phenyl]urea , (4) 1-[2-chloro-5-(trifluoromethyl)-3-pyridyl]-3-(2-{4-[2-(2-o-oxy-1-pyrrolidinyl) -1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (5) 1-(2-{4-[2-(2-o-oxy-1-pyrrolidinyl) -1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-[5-(trifluoromethyl)-3-pyridyl]urea, (6) 1-[3-hydroxyl -5-(Trifluoromethyl)phenyl]-3-(2-{4-[2-(2-o-oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy }-5-pyrimidinyl)urea, (7) 1-(2-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3 -[4-(Trifluoromethyl)-2-pyridyl]urea, (8) 2-{[(2-{4-[2-(2-o-oxy-1-pyrrolidinyl)-1, 3-thiazol-5-yl]phenoxy}-5-pyrimidinylaminocarbamoyl]amino}-4-(trifluoromethyl)benzoic acid, (9) 1-[2-(2- Hydroxy-2-propyl)-5-(trifluoromethyl)phenyl]-3-(2-{4-[2-(2-o-oxy-1-pyrrolidinyl)-1,3-thiazole -5-yl]phenoxy}-5-pyrimidinyl)urea, (10) 1-[3,5-bis(trifluoromethyl)phenyl]-3-(2-{4-[2-( 2-sided oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (11) 1-[2-(3-hydroxy-3- Methyl-1-butyn-1-yl)-5-(trifluoromethyl)-3-pyridyl]-3-(2-{4-[2-(2-o-oxy-1-pyrrolidine) -1,3-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (12) 1-[2-(2-hydroxy-2-propyl)-5-(trifluoromethyl) Benzyl-3-pyridyl]-3-(2-{4-[2-(2-o-oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5 -pyrimidinyl)urea, (13) 1-[2-methoxy-5-(trifluoromethyl)-3-pyridyl]-3-(2-{4-[2-(2-trioxy) -1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, (14) 1-(2-{3-methyl-4-[2-( 2-sided oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl-3-[3-(trifluoromethyl)phenyl]urea, (15) 1-[2-({6-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]-3-pyridyl}oxy)-5 -pyrimidinyl]-3-[3-(trifluoromethyl)phenyl]urea, (16) 1-[2-(4-{2-[3-(2-hydroxy-2-propyl)-2 -Sideoxy-1-pyrrolidinyl]-1,3-thiazol-5-yl}phenoxy)-5-pyrimidinyl]-3-[3-(trifluoromethyl)phenyl]urea, 17) 1-[3-(Difluoromethyl)phenyl]-3-(2-{4-[2-(2-o-oxy-1-pyrrolidinyl)-1,3-thiazole-5- (Phenyloxy}-5-pyrimidinyl)urea, (18) 1-[3-(1,1-difluoroethyl)phenyl]-3-(2-{4-[2-(2- Sideoxy-1-pyrrolidinyl)- 1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, or (19)1-[2-(4-{2-[3-(2-hydroxy-2-propyl)) -2-Sideoxy-1-pyrrolidinyl]-1,3-thiazol-5-yl}phenoxy)-5-pyrimidinyl]-3-[2-(methylsulfonyl)-5- (Trifluoromethyl)phenyl]urea, a salt thereof, an N-oxide thereof, a solvate thereof or such a prodrug.

通式(I)表示之化合物中，其他之較佳化合物為(1)1-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[3-(三氟甲基)環己基]脲、(2)1-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-苯基-5-(三氟甲基)環己基]脲、(3)1-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-(3-吡啶基)-5-(三氟甲基)環己基]脲、(4)1-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[3-(3-吡啶基氧基)-5-(三氟甲基)苯基]脲、(5)N-乙基-N-[5-(4-{[5-({[2-苯基-5-(三氟甲基)-3-吡啶基]胺基甲醯基}胺基)-2-吡啶基]氧基}苯基)-1，3-噻唑-2-基]丙醯胺、(6)1-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-(3-吡啶基氧基)-5-(三氟甲基)苯基]脲、(7)1-(2-{4-[2-(二甲胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[3-(三氟甲基)苯基]脲、(8)1-[2-(環丙胺基甲醯基)-5-(三氟甲基)-3-吡啶基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(9)1-(2-{4-[2-(3-側氧基-4-嗎啉基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[3-(三氟甲基)苯基]脲、(10)1-(2-{4-[2-(二甲胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2- (3-吡啶基)-5-(三氟甲基)苯基]脲、(11)1-(6-{4-[2-(二甲胺基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)-3-[3-(三氟甲基)苯基]脲、(12)1-(2-{4-[2-(二乙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[3-(三氟甲基)苯基]脲、(13)1-(6-{4-[2-(二甲胺基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)-3-[2-(3-吡啶基)-5-(三氟甲基)苯基]脲、(14)1-[2-氯-5-(三氟甲基)苯基]-3-(2-{4-[2-(二甲胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、(15)1-{2-[4-(2-胺基-1，3-噻唑-5-基)苯氧基]-5-嘧啶基}-3-[2-(3-吡啶基)-5-(三氟甲基)苯基]脲、(16)1-[2-氯-4-(三氟甲基)苯基]-3-(6-{4-[2-(二甲胺基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)脲、(17)1-(2-{4-[2-(二丙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[3-(三氟甲基)苯基]脲、(18)1-[2-(4-{2-[乙基(甲基)胺基]-1，3-噻唑-5-基}苯氧基)-5-嘧啶基]-3-[3-(三氟甲基)苯基]脲、(19)1-[6-(4-{2-[(環丙基甲基)(甲基)胺基]-1，3-噻唑-5-基}苯氧基)-3-吡啶基]-3-[3-(三氟甲基)苯基]脲、(20)1-(2-{4-[2-(4-嗎啉基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[3-(三氟甲基)苯基]脲、(21)1-[6-(4-{2-[(環丙基甲基)(甲基)胺基]-1，3-噻唑-5-基}苯氧基)-3-吡啶基]-3-[3’，4’-二甲基-4-(三氟甲基)-2-聯苯基]脲、(22)1-[6-(4-{2-[乙基(甲基)胺基]-1，3-噻唑-5-基}苯氧基)-3-吡啶 基]-3-[3-(三氟甲基)苯基]脲、(23)1-(2-{4-[2-(二甲胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-(1H-吡唑-1-基)-5-(三氟甲基)苯基]脲、(24)1-(3，5-二氟苯基)-3-(2-{4-[2-(二甲胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、或(25)1-[2-氯-4-(三氟甲基)苯基]-3-(2-{4-[2-(二甲胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲、其鹽、其N-氧化物、其溶劑化物或該等之前驅藥。 Among the compounds represented by the formula (I), the other preferred compounds are (1) 1-(2-{4-[2-(2-o-oxy-1-pyrrolidinyl)-1,3-thiazole- 5-yl]phenoxy}-5-pyrimidinyl)-3-[3-(trifluoromethyl)cyclohexyl]urea, (2) 1-(2-{4-[2-(2- side oxygen) -ylpyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-[2-phenyl-5-(trifluoromethyl)cyclohexyl]urea , (3) 1-(2-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)- 3-[2-(3-pyridyl)-5-(trifluoromethyl)cyclohexyl]urea, (4) 1-(2-{4-[2-(2-o-oxy-1-pyrrolidine) -1,3-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-[3-(3-pyridyloxy)-5-(trifluoromethyl)phenyl]urea , (5) N-ethyl-N-[5-(4-{[5-({[2-phenyl-5-(trifluoromethyl)-3-pyridyl]aminocarbinyl)amine (2-pyridyl)oxy}phenyl)-1,3-thiazol-2-yl]propanamine, (6) 1-(2-{4-[2-(2-sideoxy-) 1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl-3-[2-(3-pyridyloxy)-5-(trifluoromethyl) Phenyl]urea, (7) 1-(2-{4-[2-(dimethylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-[ 3-(trifluoromethyl)phenyl]urea, (8) 1-[2-(cyclopropylamino) Methiol)-5-(trifluoromethyl)-3-pyridyl]-3-(2-{4-[2-(2-o-oxy-1-pyrrolidinyl)-1,3-thiazole -5-yl]phenoxy}-5-pyrimidinyl)urea, (9) 1-(2-{4-[2-(3-o-oxy-4-morpholinyl)-1,3-thiazole -5-yl]phenoxy}-5-pyrimidinyl)-3-[3-(trifluoromethyl)phenyl]urea, (10) 1-(2-{4-[2-(dimethylamine) -1,3-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl-3-[2- (3-pyridyl)-5-(trifluoromethyl)phenyl]urea, (11) 1-(6-{4-[2-(dimethylamino)-1,3-thiazol-5-yl Phenoxy}-3-pyridyl)-3-[3-(trifluoromethyl)phenyl]urea, (12) 1-(2-{4-[2-(diethylamino)-1 , 3-thiazole-5-yl]phenoxy}-5-pyrimidinyl)-3-[3-(trifluoromethyl)phenyl]urea, (13) 1-(6-{4-[2- (dimethylamino)-1,3-thiazol-5-yl]phenoxy}-3-pyridyl)-3-[2-(3-pyridyl)-5-(trifluoromethyl)phenyl Urea, (14) 1-[2-chloro-5-(trifluoromethyl)phenyl]-3-(2-{4-[2-(dimethylamino)-1,3-thiazole-5 -yl]phenoxy}-5-pyrimidinyl)urea, (15) 1-{2-[4-(2-amino-1,3-1,3-thiazol-5-yl)phenoxy]-5-pyrimidine }[-3-(3-pyridyl)-5-(trifluoromethyl)phenyl]urea, (16) 1-[2-chloro-4-(trifluoromethyl)phenyl]- 3-(6-{4-[2-(Dimethylamino)-1,3-thiazol-5-yl]phenoxy}-3-pyridyl)urea, (17) 1-(2-{4 -[2-(Dipropylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-[3-(trifluoromethyl)phenyl]urea, (18) 1-[2-(4-{2-[ethyl(methyl)amino]-1,3-thiazol-5-yl}phenoxy)-5-pyrimidinyl]-3-[3-(three Fluoromethyl)phenyl]urea, (19) 1-[6-(4-{2-[(cyclopropylmethyl)(methyl)amino]-1,3-thiazol-5-yl}benzene (3-pyridyl)-3-[3-(trifluoromethyl)phenyl]urea, (20) 1-(2-{4-[2-(4-morpholinyl)-1,3 -thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-[3-(trifluoromethyl)phenyl]urea, (21) 1-[6-(4-{2-[( Cyclopropylmethyl)(methyl)amino]-1,3-thiazol-5-yl}phenoxy)-3-pyridyl]-3-[3',4'-dimethyl-4- (trifluoromethyl)-2-biphenyl]urea, (22) 1-[6-(4-{2-[ethyl(methyl)amino]-1,3-thiazol-5-yl} Phenoxy)-3-pyridine 3-[3-(trifluoromethyl)phenyl]urea, (23) 1-(2-{4-[2-(dimethylamino)-1,3-thiazol-5-yl] Phenoxy}-5-pyrimidinyl-3-[2-(1H-pyrazol-1-yl)-5-(trifluoromethyl)phenyl]urea, (24) 1-(3,5- Difluorophenyl)-3-(2-{4-[2-(dimethylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea, or (25) 1-[2-chloro-4-(trifluoromethyl)phenyl]-3-(2-{4-[2-(dimethylamino)-1,3-thiazol-5-yl]phenoxy }-5-pyrimidinyl)urea, a salt thereof, an N-oxide thereof, a solvate thereof, or such a prodrug.

於本發明，若無特別指示下則，包含所有之異構體。例如包含烷基、烷氧基、烯基及伸烷基等之直鏈者及支鏈者。另，雙鍵、環、稠環之異構體(E、Z、順式、反式體)、因不對稱碳原子存在產生之異構體(R、S體、α、β體、鏡像異構物、非鏡像異構物)、具有旋光性之光學活性物(D、L、d、l體)、經由層析儀分離之極性體(高極性體、低極性體)、平衡化合物、旋轉異構體、該等任意比例之混合物、消旋混合物均包含於本發明中。又，於本發明，包含所有因互變異性產生之異構體。 In the present invention, all isomers are included unless otherwise specified. For example, a linear group and a branched chain including an alkyl group, an alkoxy group, an alkenyl group, and an alkylene group. In addition, isomers of double bonds, rings, and fused rings (E, Z, cis, trans), isomers due to the presence of asymmetric carbon atoms (R, S, α, β, mirror Structure, non-image isomer), optically active optically active substance (D, L, d, l body), polar body separated by a chromatograph (high polarity body, low polarity body), equilibrium compound, rotation Isomers, mixtures of such ratios, and racemic mixtures are all included in the present invention. Further, in the present invention, all isomers resulting from mutual variability are included.

於本發明，若無特別說明，業者都明瞭符號 In the present invention, unless otherwise stated, the operator has clearly defined the symbols.

表示結合於往紙面另一側(亦即α-配置)，符號 Indicates that the symbol is bonded to the other side of the paper (ie, α-configuration), the symbol

表示結合於往紙面前側(亦即β配置)，符號 Indicates the combination of the symbol on the front side of the paper (also known as the beta configuration), the symbol

表示為α-配置或β-配置，符號 Expressed as alpha-configuration or beta-configuration, symbol

表示α-配置與β-配置之混合物。 Represents a mixture of alpha-configuration and beta-configuration.

[鹽] [salt]

通式(I)表示之化合物以公知之方法轉換為鹽。 The compound represented by the formula (I) is converted into a salt by a known method.

鹽較好為藥學上容許之鹽。 The salt is preferably a pharmaceutically acceptable salt.

鹽較好為水溶性鹽。 The salt is preferably a water soluble salt.

鹽可列舉例如鹼金屬鹽、鹼土金屬鹽、銨鹽、胺鹽或酸加成鹽等。 The salt may, for example, be an alkali metal salt, an alkaline earth metal salt, an ammonium salt, an amine salt or an acid addition salt.

鹼金屬鹽可列舉例如鉀及鈉等。 Examples of the alkali metal salt include potassium and sodium.

鹼土金屬鹽可列舉例如鈣及鎂等。 Examples of the alkaline earth metal salt include calcium and magnesium.

銨鹽可列舉例如四甲基銨等。 The ammonium salt may, for example, be tetramethylammonium or the like.

胺鹽可列舉例如三乙胺、甲胺、二甲胺、環戊胺、苄胺、苯乙胺、哌啶、一乙醇胺、二乙醇胺、三(羥基甲基)胺基甲烷、賴胺酸、精胺酸及N-甲基-D-還原葡糖胺等。 The amine salt may, for example, be triethylamine, methylamine, dimethylamine, cyclopentylamine, benzylamine, phenethylamine, piperidine, monoethanolamine, diethanolamine, tris(hydroxymethyl)aminomethane, lysine, Arginine and N-methyl-D-reduced glucosamine, and the like.

酸加成鹽可列舉例如如鹽酸鹽、氫溴酸鹽、氫碘酸鹽、硫酸鹽、磷酸鹽、硝酸鹽之無機酸鹽或如酢酸鹽、乳酸鹽、酒石酸鹽、苯甲酸鹽、檸檬酸鹽、甲磺酸鹽、乙磺酸鹽、三氟乙酸鹽、苯磺酸鹽、甲苯磺酸鹽、羥乙磺酸鹽、葡糖醛酸鹽或葡糖酸鹽之有機酸鹽。 The acid addition salt may, for example, be a mineral acid salt such as a hydrochloride, a hydrobromide, a hydroiodide, a sulfate, a phosphate or a nitrate or a salt such as a citrate, a lactate, a tartrate or a benzoate. An organic acid salt of citrate, methanesulfonate, ethanesulfonate, trifluoroacetate, besylate, tosylate, isethionate, glucuronate or gluconate.

又，本發明化合物可以任意方法形成N-氧化物。N- 氧化物表示通式(I)表示之化合物之氮原子經氧化者，例如於通式(I)表示之化合物中之A1、A2、A3、A4、A5或A6各自獨立為=N-時，該氮原子經氧化者。或Cy1及Cy2各自獨立為含氮雜環時，該氮原子經氧化者。另，R2基及R6基各自獨立為具有-NH(C1至3烷基)及-N(C1至3烷基)2之基時，該氮原子經氧化者。又，Z基之氮原子及噻唑環之氮原子經氧化者。 Further, the compound of the present invention can be formed into an N-oxide by any method. The N-oxide represents a oxidized nitrogen atom of the compound represented by the formula (I), for example, each of A 1 , A 2 , A 3 , A 4 , A 5 or A 6 in the compound represented by the formula (I) When independently ==N-, the nitrogen atom is oxidized. Or when Cy 1 and Cy 2 are each independently a nitrogen-containing heterocyclic ring, the nitrogen atom is oxidized. Further, when the R 2 group and the R 6 group are each independently a group having -NH(C1 to 3 alkyl group) and -N(C1 to 3 alkyl group) 2 , the nitrogen atom is oxidized. Further, the nitrogen atom of the Z group and the nitrogen atom of the thiazole ring are oxidized.

通式(I)表示之化合物及其鹽可轉換為溶劑化物。 The compound represented by the formula (I) and a salt thereof can be converted into a solvate.

溶劑化物較好為無毒性且為水溶性。適當之溶劑化物可列舉例如水或如醇系溶劑(例如乙醇等)之溶劑化物。 The solvate is preferably non-toxic and water soluble. Suitable solvates include, for example, water or a solvate such as an alcohol solvent (e.g., ethanol).

[前驅藥] [precursor]

通式(I)表示之化合物之前驅藥為於生體內經由酵素或胃酸等之反應而，轉換為通式(I)表示之化合物之化合物。通式(I)表示之化合物之前驅藥可列舉例如通式(I)表示之化合物具有胺基時，為該胺基經醯基化、烷基化、磷酸化之化合物(例如通式(I)表示之化合物之胺基經二十烷醯基化、丙胺醯基化、戊胺基羰基化、(5-甲基-2-側氧基-1，3-二茂烷-4-基)甲氧基羰基化、四氫呋喃基化、吡咯啶基甲基化、三甲基乙醯氧基甲基化、乙醯氧基甲基化、第三丁基化之化合物等)；通式(I)表示之化合物具有羥基時，為該羥基經醯基化、烷基化、磷酸化、硼酸化之化合物(例如通式(I)表示之化合物之羥基經乙醯基化、棕櫚醯基化、丙醯基化、三甲基乙醯基化、琥珀醯基化、富馬醯基化、丙胺醯基化、二甲胺基甲基羰基化之化合物等)；通式(I)表示之化合物具有羧基時，為該羧基經酯化、醯胺化之化合物(例如通式(I)表示之化合物之羧基經乙基酯化、苯基酯化、羧基甲基酯化、二甲胺基甲基酯化、三甲基乙 醯氧基甲基酯化、1-{(乙氧基羰基)氧基}乙基酯化、酞酮基酯化、(5-甲基-2-側氧基-1，3-二茂烷-4-基)甲基酯化、1-{[(環己基氧基)羰基]氧基}乙基酯化、甲基醯胺化之化合物等)等。該等化合物可經由其自體所公知之方法製造。又，通式(I)表示之化合物之前驅藥可為水和物及非水和物中之任何一種。此外，通式(I)表示之化合物之前驅藥亦可為以如廣川書店1990年刊「醫藥品之開發」第7卷「分子設計」163至198頁中記載之再生理條件轉換為通式(I)表示之化合物者。 The compound represented by the formula (I) is a compound which is converted into a compound represented by the formula (I) by a reaction of an enzyme or gastric acid in a living body. When the compound represented by the formula (I) has an amine group, the compound represented by the formula (I) is a compound which is thiolated, alkylated, or phosphorylated (for example, the formula (I) The amine group of the compound represented by eicosyl oximation, propylamine thiolation, pentylaminocarbonylation, (5-methyl-2- oxo-1,3-di Methoxy-4-yl)methoxycarbonylation, tetrahydrofuranylation, pyrrolidinylmethylation, trimethylacetoxymethylation, ethoxymethylation, tert-butylation When the compound represented by the formula (I) has a hydroxyl group, the compound which is thiolated, alkylated, phosphorylated or borated is (for example, the hydroxyl group of the compound represented by the formula (I) is ethoxylated. , palmitoylation, propylation, trimethylacetylation, amber thiolation, fumarylation, propylamine thiolation, dimethylaminomethylcarbonylation, etc.); When the compound represented by I) has a carboxyl group, the compound which is esterified or amided with the carboxyl group (for example, the carboxyl group of the compound represented by the formula (I) is ethyl esterified, phenyl esterified, or carboxymethyl esterified, Dimethylaminomethyl esterification, trimethylacetoxymethyl esterification, 1-{(ethoxycarbonyl)oxy}ethyl esterification, anthosterone esterification, (5-methyl- 2-sided oxy-1,3-di Multane-4-yl)methyl esterification, 1-{[(cyclohexyloxy)carbonyl]oxy}ethyl esterification, methylammonium compound, etc.). These compounds can be produced by methods known per se. Further, the compound represented by the formula (I) may be any one of water and non-aqueous substances. In addition, the prodrug of the compound represented by the general formula (I) may be converted into a general formula by re-physiological conditions as described in the "Development of Pharmaceutical Products", Vol. 7, "Molecular Design", Guangchuan Bookstore, Vol. 7, 1990. I) The compound indicated.

另，構成通式(I)表示之化合物之各原子亦可經其同位元素(例如2H、3H、13C、14C、15N、16N、17O、18O、35S、125I等)等取代。 Further, each atom constituting the compound represented by the general formula (I) may also pass through its isotopic element (for example, 2 H, 3 H, 13 C, 14 C, 15 N, 16 N, 17 O, 18 O, 35 S, 125 I, etc.) replaced.

[本發明化合物之製造方法] [Method for Producing Compound of the Present Invention]

通式(I)表示之本發明化合物可以公知之方法，例如根據以下表示之方法、以該等方法為基準之方法或實施例中表示之方法製造。又，於以下之各製造方法中，原料化合物可作為鹽使用。該等鹽使用記載為通式(I)藥學上容許之鹽者。 The compound of the present invention represented by the formula (I) can be produced by a known method, for example, according to the method shown below, the method based on the methods, or the method represented by the examples. Further, in each of the following production methods, the raw material compound can be used as a salt. These salts are described as being pharmaceutically acceptable salts of the formula (I).

通式(I)中之Y為氧原子或可經氧化之硫原子之本發明化合物可以例如以下反應步驟式1表示之方法製造。 The compound of the present invention wherein Y in the formula (I) is an oxygen atom or an oxidizable sulfur atom can be produced, for example, by the method represented by the following reaction scheme.

(式中，L-a表示鹵素原子，M-a表示鹵素原子、硼酸基(-B(OH)2)或硼酸酯基(-B(ORi)(ORii)(式中，Ri及Rii表示C1至3烷基，Ri及Rii可一同形成環)，例如4，4，5，5-四甲基-1，3，2-二氧基硼烷-2-基等)，Y-a表示氧原子或硫原子，Y-b表示氧原子、硫原子或經氧化之硫原子，L-b表示鹵素原子或氫原子，其他符號與上述[1]記載之符號同意義。) (wherein, La represents a halogen atom, Ma represents a halogen atom, a boronic acid group (-B(OH) 2 ) or a boronic acid ester group (-B(ORi)(ORii) (wherein Ri and Rii represent a C1 to 3 alkane) a group, Ri and Ri may form a ring together, for example, 4,4,5,5-tetramethyl-1,3,2-dioxaboran-2-yl, etc., and Ya represents an oxygen atom or a sulfur atom. Yb represents an oxygen atom, a sulfur atom or an oxidized sulfur atom, and Lb represents a halogen atom or a hydrogen atom, and other symbols have the same meaning as the symbols described in the above [1].)

又，通式(Ⅵ)表示之化合物中，Y-b經氧化之硫原子之化合物，可由將於上述反應步驟式1中Y-a為硫原子且，經醚化反應後獲得之化合物以公知之方法氧化而，製造。 Further, in the compound represented by the formula (VI), the compound in which the sulfur atom of Yb is oxidized may be oxidized by a known method by a compound obtained by subjecting Ya to a sulfur atom in the above reaction step and having an etherification reaction. , manufacturing.

又，具有羧基、膦醯基氧基、羥基及胺基之本發明化合物視需要可使用以對於該等基以廣泛使用之保護基，例如「Comprehensive Organic Transformations：A Guide to Functional Group Preparations 2nd Edition(Richard C.Larock，John Wiley & Sons Inc，1999)」中記載之保護基保護之化合物，進行至上述反應步驟式1中記載之脲化反應為止之反應後，進行公知之脫保護反應，或進行例如「Comprehensive Organic Transformations：A Guide to Functional Group Preparations 2nd Edition(Richard C.Larock，John Wiley & Sons Inc，1999)」中記載之脫保護反應製造。 Further, the compound of the present invention having a carboxyl group, a phosphinyloxy group, a hydroxyl group and an amine group may be optionally used as a protecting group widely used for such groups, for example, "Comprehensive Organic Transformations: A Guide to Functional" The compound protected by the protecting group described in Group Preparations 2nd Edition (Richard C. Larock, John Wiley & Sons Inc, 1999) is subjected to the reaction up to the urea-forming reaction described in the above Reaction Scheme 1, and then known to be removed. The protective reaction is carried out, for example, by a deprotection reaction described in "Comprehensive Organic Transformations: A Guide to Functional Group Preparations 2nd Edition (Richard C. Larock, John Wiley & Sons Inc, 1999)".

於反應步驟式1中，從通式(Ⅱ)表示之化合物製造通式(Ⅲ)表示之化合物之反應步驟(胺基甲酸酯化反應)為公知之方法。經由該反應獲得之通式(Ⅲ)表示之化合物可經由例如使用通式(Ⅱ)表示之化合物及2，2，2-三氯乙氧基羰基氯化物，於有機溶劑(例如吡啶、乙酸乙酯、二氯甲烷、二烷、二乙醚或將該等有機溶劑適當混合之溶劑等)或該等有機溶劑與水之混合溶劑中，在鹼(例如4-二甲胺基吡啶、吡啶、三乙胺、碳酸氫鈉等)存在或不存在下，於約-20℃至80℃之溫度進行反應而製造。 In the reaction scheme, the reaction step (urementation reaction) of the compound represented by the formula (III) from the compound represented by the formula (II) is a known method. The compound represented by the formula (III) obtained by the reaction can be, for example, a compound represented by the formula (II) and 2,2,2-trichloroethoxycarbonyl chloride in an organic solvent (for example, pyridine, acetic acid B). Ester, dichloromethane, two a solvent in which an alkane, diethyl ether or an organic solvent is appropriately mixed, or the like, or a mixed solvent of the organic solvent and water, in a base (for example, 4-dimethylaminopyridine, pyridine, triethylamine, sodium hydrogencarbonate, etc.) Manufactured in the presence or absence of a reaction at a temperature of about -20 ° C to 80 ° C.

於反應步驟式1中，從通式(Ⅳ)表示之化合物製造通式(Ⅵ)表示之化合物之反應步驟(醚化反應、還原反應)為公知之方法。經由該反應獲得之通式(Ⅵ)表示之化合物可經由例如將使用通式(Ⅳ)表示之化合物及通式(V)表示之化合物，於有機溶劑(例如二甲亞碸、二甲基甲醯胺、甲醇、乙腈或將該等有機溶劑適當混合之溶劑等)或該等有機溶劑與水之混合溶劑中，在鹼(例如氟化鉀、碳酸鉀、磷酸三鉀、氫氧化鈉、氫化鈉等)存在下，於約0℃至120℃之溫度進行反應獲得之化合物，於氫氣環境下，於有機溶劑(例如甲醇、乙醇、乙酸乙酯、四氫呋喃、乙酸、1，2-二甲氧基乙烷或將該等有機溶劑適當混合之溶劑等)或該等有機溶劑 與水之混合溶劑中，於觸媒(例如銀觸媒(例如乙酸銀等)、鉑觸媒(例如鉑-碳、氧化鉑等)、銠觸媒(例如銠-碳等)、鐵觸媒(例如乙酸鐵等)、釕觸媒(例如釕-碳等)、鈀觸媒(例如鈀-碳等)、鋅觸媒(溴化鋅、碘化鋅、乙酸鋅等)、雷氏鎳(Raney nickel)或將該等觸媒適當混合之觸媒等)存在下，於室溫至約80℃之溫度進行反應或於有機溶劑(例如乙酸、鹽酸、乙醇、甲醇、二甲基甲醯胺、甲苯或將該等有機溶劑適當混合之溶劑等)或該等有機溶劑與水之混合溶劑中，於觸媒(例如鐵觸媒(例如鐵、氯化鐵、鐵-氯化銨等)、鋅觸媒(例如鋅等)、鎳觸媒(例如氯化鎳等)、銦觸媒(例如銦等)、錫觸媒(例如錫、氯化錫等)或將該等觸媒適當混合之觸媒等)存在下，於室溫至約80℃之溫度進行反應製造。 In the reaction scheme, the reaction step (etherification reaction, reduction reaction) of the compound represented by the formula (VI) from the compound represented by the formula (IV) is a known method. The compound represented by the formula (VI) obtained by the reaction can be, for example, a compound represented by the formula (IV) and a compound represented by the formula (V) in an organic solvent (for example, dimethyl hydrazine, dimethyl ketone). a solvent such as guanamine, methanol, acetonitrile or a suitable solvent for mixing the organic solvents, or a mixed solvent of the organic solvent and water, in a base (for example, potassium fluoride, potassium carbonate, tripotassium phosphate, sodium hydroxide, hydrogenation) a compound obtained by reacting at a temperature of about 0 ° C to 120 ° C in the presence of sodium or the like, in an organic solvent such as methanol, ethanol, ethyl acetate, tetrahydrofuran, acetic acid, 1,2-dimethoxygen under a hydrogen atmosphere. a solvent or the like in which the organic solvent is appropriately mixed, or the organic solvent In a mixed solvent with water, a catalyst (for example, a silver catalyst (for example, silver acetate), a platinum catalyst (for example, platinum-carbon, platinum oxide, etc.), a ruthenium catalyst (for example, ruthenium-carbon, etc.), and an iron catalyst. (e.g., iron acetate, etc.), ruthenium catalyst (e.g., ruthenium-carbon, etc.), palladium catalyst (e.g., palladium-carbon, etc.), zinc catalyst (zinc bromide, zinc iodide, zinc acetate, etc.), Reynolds nickel ( Raney nickel) or a suitable catalyst for mixing such catalysts, etc., at room temperature to about 80 ° C or in an organic solvent (eg acetic acid, hydrochloric acid, ethanol, methanol, dimethylformamide) a toluene or a solvent in which the organic solvents are appropriately mixed, or a mixed solvent of the organic solvent and water, in a catalyst (for example, an iron catalyst (for example, iron, ferric chloride, iron-ammonium chloride, etc.), a zinc catalyst (such as zinc), a nickel catalyst (such as nickel chloride), an indium catalyst (such as indium), a tin catalyst (such as tin, tin chloride, etc.) or a suitable mixture of the catalysts The reaction is carried out at a temperature of from room temperature to about 80 ° C in the presence of a catalyst or the like.

於反應步驟式1中，從通式(Ⅵ)表示之化合物製造通式(Ⅷ)表示之化合物之反應步驟(芳基化反應)為公知之方法。經由該反應獲得之通式(Ⅷ)表示之化合物可經由例如將使用通式(Ⅵ)表示之化合物及通式(Ⅶ)表示之化合物，於有機溶劑(例如二甲基乙醯胺、二甲基甲醯胺、醇(例如甲醇、乙醇等)、二乙基羧酸酯、二烷、1，2-二甲氧基乙烷、甲苯或將該等有機溶劑適當混合之溶劑等)或該等有機溶劑與水之混合溶劑中，於鹼(例如碳酸銫、乙酸鉀、碳酸鉀、碳酸鈉、第三丁醇鋰、碳酸銀、磷酸三鉀、三乙胺或將該等鹼適當混合之鹼等)存在下或不存在下，於觸媒(例如鈀觸媒(例如氧化鈀、乙酸鈀、雙(三-第三丁基膦)鈀、鈀(O)四(三苯基膦)、雙(三苯基膦)二氯鈀(Ⅱ)或將該等觸媒適當混合之觸媒等))中，於室溫至約120℃之溫度進行反應製造。 In the reaction scheme, the reaction step (arylation reaction) of the compound represented by the formula (VIII) from the compound represented by the formula (VI) is a known method. The compound represented by the formula (VIII) obtained by the reaction can be, for example, a compound represented by the formula (VI) and a compound represented by the formula (VII) in an organic solvent (for example, dimethylacetamide, dimethyl Mercaptoamine, alcohol (eg methanol, ethanol, etc.), diethyl carboxylate, two Alkane, 1,2-dimethoxyethane, toluene or a solvent in which the organic solvents are appropriately mixed, or the like, or a mixed solvent of the organic solvent and water, in a base (for example, cesium carbonate, potassium acetate, potassium carbonate) a catalyst (for example, palladium oxide) in the presence or absence of sodium carbonate, lithium butoxide, silver carbonate, tripotassium phosphate, triethylamine or a base in which the bases are appropriately mixed, etc. , palladium acetate, bis(tri-tert-butylphosphine)palladium, palladium (O) tetrakis(triphenylphosphine), bis(triphenylphosphine)dichloropalladium(II) or a suitable mixture of the catalysts In a catalyst or the like), the reaction is carried out at a temperature of from room temperature to about 120 °C.

於反應步驟式1中，從通式(Ⅷ)表示之化合物製造通 式(I’)表示之本發明化合物之反應步驟(脲化反應)為使用通式(Ⅷ)表示之化合物及通式(Ⅲ)表示之化合物進行之反應，可於以本說明書中記載之實施例之條件或公知之條件下進行。 In the reaction step formula 1, the compound represented by the formula (VIII) is produced. The reaction step (ureaturization reaction) of the compound of the present invention represented by the formula (I') is carried out by using the compound represented by the formula (VIII) and the compound represented by the formula (III), and can be carried out as described in the present specification. Under the conditions of the examples or under known conditions.

於反應步驟式1中，作為出發原料使用之通式(Ⅱ)、(Ⅳ)、(V)及(Ⅶ)表示之化合物為公知者，或經由使用公知之方法，例如「Comprehensive Organic Transformations：A Guide to Functional Group Preparations 2nd Edition(Richard C.Larock，John Wiley & Sons Inc，1999)」中記載之方法，可容易的製造。 In the reaction scheme, the compounds represented by the formulae (II), (IV), (V) and (VII) used as starting materials are known, or by using a known method, for example, "Comprehensive Organic Transformations: A The method described in Guide to Functional Group Preparations 2nd Edition (Richard C. Larock, John Wiley & Sons Inc, 1999) can be easily produced.

又，通式(I)中之Y為氧原子或可經氧化之硫原子之本發明化合物，亦可經由例如為另一方法之使用由上述反應步驟式1中之通式(Ⅷ)表示之化合物及2，2，2-三氯乙氧基羰氯化物製造之2，2，2-三氯乙基胺基甲酸酯衍生物，與通式(Ⅱ)表示之化合物進行脲化反應而製造。 Further, the compound of the present invention wherein Y in the formula (I) is an oxygen atom or an oxidizable sulfur atom may be represented by the above formula (VIII) in the above reaction step, for example, by another method. a compound and a 2,2,2-trichloroethylcarbamate derivative produced by 2,2,2-trichloroethoxycarbonyl chloride, which is subjected to a urea reaction with a compound represented by the formula (II) Manufacturing.

另，通式(I)中之Y為亞甲基之本發明化合物，例如可由使用以下反應步驟式2中通式(XI)表示之化合物取代上述反應步驟式1中通式(Ⅵ)表示之化合物，經由與反應步驟式1相同之反應步驟製造。 Further, the compound of the present invention wherein Y in the formula (I) is a methylene group can be represented, for example, by substituting the compound represented by the formula (XI) in the following reaction scheme of the formula 2 in the above reaction step, in the formula (VI) of the above formula. The compound was produced by the same reaction procedure as in Reaction Scheme 1.

(式中，L-c表示脫離基(例如鹵素原子、甲磺酸酯或三氟 甲磺酸酯等)，M-b表示鹵素原子，W-b表示硼酸基(-B(OH)2)或硼酸酯基(-B(ORi)(ORii)(式中，Ri及Rii表示C1至3烷基，Ri及Rii可一同形成環)，例如4，4，5，5-四甲基-1，3，2-二氧基硼烷-2-基等)或烷基錫基(例如三丁基錫等)，其他符號與上述[1]記載之符號同意義。) (wherein, Lc represents a leaving group (for example, a halogen atom, a mesylate or a triflate, etc.), Mb represents a halogen atom, and Wb represents a boronic acid group (-B(OH) 2 ) or a boronic acid ester group ( -B(ORi)(ORii) (wherein, Ri and Rii represent a C1 to 3 alkyl group, and Ri and Ri may together form a ring), for example, 4,4,5,5-tetramethyl-1,3,2- a dioxaboran-2-yl group or the like, or an alkyl tin group (for example, tributyltin or the like), and other symbols have the same meanings as the symbols described in the above [1].)

於反應步驟式2中，從通式(Ⅸ)表示之化合物製造通式(XI)表示之化合物之反應步驟(偶合反應、還原反應)為公知之方法。經由該反應獲得之通式(XI)表示之化合物，可經由例如使用通式(Ⅸ)表示之化合物及通式(X)表示之化合物，於有機溶劑(例如二甲基乙醯胺、二甲基甲醯胺、醇(例如甲醇、乙醇等)、二乙基羧酸酯、二烷、1，2-二甲氧基乙烷、甲苯、二甲苯、四氫呋喃、二氯甲烷、丙酮、乙腈或將該等有機溶劑適當混合之溶劑等)或該等有機溶劑與水之混合溶劑中，於鹼(例如碳酸銫、乙酸鉀、碳酸鉀、碳酸鈉、第三丁醇鋰、碳酸銀、磷酸三鉀、三乙胺或將該等鹼適當混合之鹼等)存在下或不存在下，於觸媒(例如鈀觸媒(例如氫氧化鈀、乙酸鈀、雙(三-第三丁基膦)鈀、鈀(O)四(三苯基膦)、雙(三苯基膦)二氯鈀(Ⅱ)或將該等觸媒適當混合之觸媒等))中，於室溫至約120℃之溫度進行反應獲得之化合物，於氫氣環境下，於有機溶劑(例如甲醇、乙醇、乙酸乙酯、四氫呋喃、乙酸、1，2-二甲氧基乙烷或將該等有機溶劑適當混合之溶劑等)或該等有機溶劑與水之混合溶劑中，於(例如銀觸媒(例如乙酸銀等)、鉑觸媒(例如鉑-碳、氧化鉑等)、銠觸媒(例如銠-碳等)、鐵觸媒(例如乙酸鐵等)、釕觸媒(例如釕-碳等)、鈀觸媒(例如鈀-碳等)、鋅觸媒(溴化鋅、碘化鋅、乙酸鋅等)、雷氏鎳或將該等觸媒適當混合之觸媒等) 存在下，於室溫至約80℃之溫度進行反應或於有機溶劑(例如乙酸、鹽酸、乙醇、甲醇、二甲基甲醯胺、甲苯或將該等有機溶劑適當混合之溶劑等)或該等有機溶劑與水之混合溶劑中，於觸媒(例如鐵觸媒(例如鐵、氯化鐵、鐵-氯化銨等)、鋅觸媒(例如鋅等)、鎳觸媒(例如氯化鎳等)、銦觸媒(例如銦等)、錫觸媒(例如錫、氯化錫等)或將該等觸媒適當混合之觸媒等)存在下，於室溫至約80℃之溫度進行反應製造。 In the reaction scheme, the reaction step (coupling reaction, reduction reaction) of the compound represented by the formula (XI) from the compound represented by the formula (IX) is a known method. The compound represented by the formula (XI) obtained by the reaction can be, for example, a compound represented by the formula (IX) and a compound represented by the formula (X) in an organic solvent (for example, dimethylacetamide, dimethyl Mercaptoamine, alcohol (eg methanol, ethanol, etc.), diethyl carboxylate, two Alkane, 1,2-dimethoxyethane, toluene, xylene, tetrahydrofuran, dichloromethane, acetone, acetonitrile or a solvent in which the organic solvents are appropriately mixed, or the like, or a mixed solvent of the organic solvent and water In the presence or absence of a base such as cesium carbonate, potassium acetate, potassium carbonate, sodium carbonate, lithium hexabutoxide, silver carbonate, tripotassium phosphate, triethylamine or a base in which the bases are appropriately mixed, etc. In a catalyst (such as palladium catalyst (such as palladium hydroxide, palladium acetate, bis(tri-tert-butylphosphine) palladium, palladium (O) tetrakis(triphenylphosphine), bis(triphenylphosphine) II a compound obtained by reacting palladium (II) chloride or a catalyst which is appropriately mixed with the catalyst, etc.), at a temperature of from room temperature to about 120 ° C, in an organic solvent (for example, methanol, ethanol, under a hydrogen atmosphere). Ethyl acetate, tetrahydrofuran, acetic acid, 1,2-dimethoxyethane or a solvent in which the organic solvents are appropriately mixed, or the like, or a mixed solvent of the organic solvent and water, for example (for example, a silver catalyst (for example) Silver acetate, etc., platinum catalyst (such as platinum-carbon, platinum oxide, etc.), ruthenium catalyst (such as ruthenium-carbon, etc.), iron catalyst (such as iron acetate, etc.)钌 catalyst (such as 钌-carbon, etc.), palladium catalyst (such as palladium-carbon, etc.), zinc catalyst (zinc bromide, zinc iodide, zinc acetate, etc.), nickel ray or appropriate mixing of these catalysts In the presence of a catalyst or the like, the reaction is carried out at a temperature of from room temperature to about 80 ° C or in an organic solvent such as acetic acid, hydrochloric acid, ethanol, methanol, dimethylformamide, toluene or the like. a solvent or the like, or a mixed solvent of the organic solvent and water, in a catalyst (for example, an iron catalyst (for example, iron, ferric chloride, iron-ammonium chloride, etc.), a zinc catalyst (for example, zinc, etc.), and a nickel contact. In the presence of a medium (such as nickel chloride), an indium catalyst (such as indium), a tin catalyst (such as tin, tin chloride, etc.) or a suitable catalyst for mixing the catalyst, etc., at room temperature The reaction was carried out at a temperature of about 80 °C.

於反應步驟式2中，作為出發原料使用之通式(IX)及(X)表示之化合物為公知，或經由使用公知之方法，例如「Comprehensive Organic Transformations：A Guide to Functional Group Preparations 2nd Edition(Richard C.Larock，John Wiley & Sons Inc，1999)」中記載之方法，可容易的製造。 In the reaction scheme, the compounds represented by the general formulae (IX) and (X) used as starting materials are known, or by using a known method, for example, "Comprehensive Organic Transformations: A Guide to Functional Group Preparations 2nd Edition (Richard) The method described in C. Larock, John Wiley & Sons Inc, 1999) can be easily manufactured.

又，通式(I)中之Y為C=O之本發明化合物例如可由使用以下反應步驟式3中通式(XⅣ)表示之化合物取代上述反應步驟式1中通式(Ⅵ)表示之化合物，經由與反應步驟式1相同之反應步驟製造。 Further, the compound of the present invention wherein Y in the formula (I) is C=O can be substituted, for example, by using the compound represented by the formula (XIV) in the following reaction scheme, in the above reaction step, in the compound represented by the formula (VI) in the above-mentioned reaction step. It is produced through the same reaction step as in Reaction Scheme 1.

(式中，M-c表示鹵素原子，其他符號與上述[1]記載之符號同意義。) (wherein, M-c represents a halogen atom, and other symbols have the same meaning as the symbols described in the above [1].)

於反應步驟式3中，從通式(XⅡ)表示之化合物製造通式(XⅣ)表示之化合物之反應步驟(弗里德爾-克拉夫茨(Friedel-Crafts)反應、還原反應)為公知之方法。經由該反應獲得之通式(XⅣ)表示之化合物，可經由例如使用通式(XⅡ)表示之化合物及通式(XⅢ)表示之化合物，於有機溶劑(例如二氯乙烷、三氟甲磺酸、硝基甲烷等)或無溶劑中，於觸媒(例如氯化鋁、硫酸鐵、三氟甲磺酸鉿、三氟甲磺酸鉍或將該等觸媒適當混合之觸媒等)中，於室溫至約150℃之溫度進行反應獲得之化合物，於氫氣環境下，於有機溶劑(例如甲醇、乙醇、乙酸乙酯、四氫呋喃、乙酸、1，2-二甲氧基乙烷或將該等有機溶劑適當混合之溶劑等)或該等有機溶劑與水之混合溶劑中，於觸媒(例如銀觸媒(例如乙酸銀等)、鉑觸媒(例如鉑-碳、氧化鉑等)、銠觸媒(例如銠-碳等)、鐵觸媒(例如乙酸鐵等)、釕觸媒(例如釕-碳等)、鈀觸媒(例如鈀-碳等)、鋅觸媒(溴化鋅、碘化鋅、乙酸鋅等)、雷氏鎳或將該等觸媒適當混合之觸媒等)存在下，於室溫至約80℃之溫度進行反應或於有機溶劑(例如乙酸、鹽酸、乙醇、甲醇、二甲基甲醯胺、甲苯或將該等有機溶劑適當混合之溶劑等)或該等有機溶劑與水之混合溶劑中，於觸媒(例如鐵觸媒(例如鐵、氯化鐵、鐵-氯化銨等)、鋅觸媒(例如鋅等)、鎳觸媒(例如氯化鎳等)、銦觸媒(例如銦等)、錫觸媒(例如錫、氯化錫等)或將該等觸媒適當混合之觸媒等)存在下，於室溫至約80℃之溫度進行反應製造。 In the reaction step 3, a reaction step (Friedel-Crafts reaction, reduction reaction) for producing a compound represented by the general formula (XIV) from a compound represented by the general formula (XII) is a known method. . The compound represented by the formula (XIV) obtained by the reaction can be, for example, a compound represented by the formula (XII) and a compound represented by the formula (XIII) in an organic solvent (for example, dichloroethane or trifluoromethanesulfonate). In acid or nitromethane, or in a solvent-free medium, such as aluminum chloride, iron sulfate, ytterbium triflate, ytterbium triflate or a suitable catalyst for mixing such catalysts, etc. a compound obtained by reacting at a temperature of from room temperature to about 150 ° C under an atmosphere of hydrogen in an organic solvent such as methanol, ethanol, ethyl acetate, tetrahydrofuran, acetic acid, 1,2-dimethoxyethane or a solvent (such as a solvent in which the organic solvent is appropriately mixed) or a mixed solvent of the organic solvent and water, in a catalyst (for example, a silver catalyst (for example, silver acetate) or a platinum catalyst (for example, platinum-carbon, platinum oxide, etc.) ), ruthenium catalyst (such as ruthenium-carbon, etc.), iron catalyst (such as iron acetate, etc.), ruthenium catalyst (such as ruthenium-carbon, etc.), palladium catalyst (such as palladium-carbon, etc.), zinc catalyst (bromine) Zinc, zinc iodide, zinc acetate, etc., Raney nickel or a suitable catalyst for mixing such catalysts, etc., at room temperature to about 80 ° C Carrying out the reaction or in an organic solvent (for example, acetic acid, hydrochloric acid, ethanol, methanol, dimethylformamide, toluene or a solvent in which the organic solvents are appropriately mixed, etc.) or a mixed solvent of the organic solvent and water, Medium (such as iron catalyst (such as iron, ferric chloride, iron-ammonium chloride, etc.), zinc catalyst (such as zinc), nickel catalyst (such as nickel chloride), indium catalyst (such as indium, etc.) The reaction is carried out at a temperature of from room temperature to about 80 ° C in the presence of a tin catalyst (for example, tin, tin chloride, or the like) or a catalyst which is appropriately mixed with the catalyst.

於反應步驟式3中，作為出發原料使用之通式(XⅡ)及(XⅢ)表示之化合物為公知，或經由使用公知之方法，例如「Comprehensive Organic Transformations：A Guide to Functional Group Preparations 2nd Edition(Richard C.Larock，John Wiley & Sons Inc，1999)」中記載之方法，可容易的製造。 In the reaction scheme, the compounds represented by the general formulae (XII) and (XIII) used as starting materials are known, or by using a known method, for example, "Comprehensive Organic Transformations: A Guide to Functional The method described in Group Preparations 2nd Edition (Richard C. Larock, John Wiley & Sons Inc, 1999) can be easily produced.

於通式(I)表示之本發明化合物中，對於上述表示之化合物以外者，可將本說明書中記載之實施例或公知之方法，例如「Comprehensive Organic Transformations：A Guide to Functional Group Preparations 2nd Edition(Richard C.Larock，John Wiley & Sons Inc，1999)」中記載之方法組合使用而，製造。 In the compound of the present invention represented by the formula (I), the examples described in the present specification or known methods, such as "Comprehensive Organic Transformations: A Guide to Functional Group Preparations 2nd Edition", may be used for the compounds other than the above-mentioned compounds. The method described in Richard C. Larock, John Wiley & Sons Inc, 1999)" was used in combination.

於本說明書中之各反應中，伴隨加熱之反應為如業者所習知，可使用水浴、油浴、砂浴或微波進行。 In the respective reactions in the present specification, the reaction accompanying heating is known to a person skilled in the art, and can be carried out using a water bath, an oil bath, a sand bath or microwave.

於本說明書中之各反應中，可適當使用附載於高分子聚合物(例如聚苯乙烯、聚丙烯基醯胺、聚丙烯、聚乙二醇等)之固體載體試藥。 In each reaction in the present specification, a solid carrier reagent attached to a polymer (for example, polystyrene, polypropylene amide, polypropylene, polyethylene glycol, or the like) can be suitably used.

於本說明書中之各反應中，反應生成物可經由通常之精製手段，例如於常壓下或減壓下蒸餾、使用矽膠或矽酸鎂之高速液體層析法、薄層層析法、離子交換樹脂、清除劑樹脂、管柱層析法或洗淨、再結晶等方法精製。精製可於每個反應進行，亦可於數個反應完成後進行。 In each reaction in the present specification, the reaction product can be subjected to usual purification means, for example, distillation under normal pressure or reduced pressure, high-speed liquid chromatography using silica gel or magnesium niobate, thin layer chromatography, ion It is refined by exchange resin, scavenger resin, column chromatography, washing or recrystallization. The refining can be carried out in each reaction or after completion of several reactions.

[毒性] [toxicity]

本發明化合物之毒性非常低。本發明化合物為未呈現例如肝毒性及消化管障害等，為腦移行性低之化合物。因此，本發明化合物作為醫藥品，可安全的使用。 The toxicity of the compounds of the invention is very low. The compound of the present invention is a compound which does not exhibit, for example, hepatotoxicity and gastrointestinal dysfunction, and is low in brain mobility. Therefore, the compound of the present invention can be used safely as a pharmaceutical.

[醫藥品之適用] [Application of pharmaceutical products]

本發明化合物由於顯示Trk阻害活性，可作為Trk阻害介在性疾病，例如疼痛、搔癢症、下部尿路障害、氣喘、過敏性鼻炎、 發炎性腸疾病或查加斯病等之預防及/或治療劑使用。 The compound of the present invention can act as a Trk-resistant disease due to the Trk inhibitory activity, such as pain, pruritus, lower urinary tract dysfunction, asthma, allergic rhinitis, Use as a prophylactic and/or therapeutic agent for inflammatory bowel disease or Chagas disease.

更具體而言，疼痛可列舉例如變形性關節炎伴隨之疼痛、癌性疼痛、慢性腰痛症、骨質粗鬆症伴隨之腰痛、骨折痛、風濕性關節炎伴隨之疼痛、神經障害性疼痛、帶狀疱疹後疼痛、糖尿病性神經障害伴隨之疼痛、纖維筋痛症、胰臟炎伴隨之疼痛、間質性膀胱炎伴隨之疼痛、子宮內膜症伴隨之疼痛、過敏性腸症候群伴隨之疼痛、偏頭痛、齒髓炎伴隨之疼痛等。搔癢症可列舉全身性皮膚搔癢症、局部性皮膚搔癢症、老人性皮膚搔癢症、妊娠搔癢症、肛門搔癢症、外陰部搔癢症等。發炎性腸疾病可列舉例如潰瘍性大腸炎、克隆氏症等。 More specifically, the pain may be, for example, pain associated with osteoarthritis, cancer pain, chronic low back pain, low back pain associated with osteoporosis, fracture pain, pain accompanying rheumatoid arthritis, and neuropathic pain. Postherpetic pain, pain associated with diabetic neurological disorders, fibromyalgia, pain associated with pancreatitis, pain associated with interstitial cystitis, pain associated with endometriosis, pain associated with irritable bowel syndrome, Migraine, pain associated with pulpitis, etc. The pruritus includes systemic pruritus, localized pruritus, pruritus of the elderly, pruritus of pregnancy, anal pruritus, and genital pruritus. Examples of the inflammatory bowel disease include ulcerative colitis, Crohn's disease, and the like.

本發明化合物作為疼痛之預防及/或治療劑特別有用。 The compounds of the invention are particularly useful as prophylactic and/or therapeutic agents for pain.

本發明化合物為了1)補齊及/或增強該化合物的預防及/或治療效果；2)改善該化合物的動態、吸收，減低投予量；及/或3)為了減輕該化合物的副作用，可與其他藥劑組合，作成併用劑而投予。 The compound of the present invention is for 1) compensating and/or enhancing the prophylactic and/or therapeutic effect of the compound; 2) improving the dynamics, absorption, and administration of the compound; and/or 3) in order to alleviate the side effects of the compound. In combination with other agents, it is administered as a co-agent.

本發明化合物與其他藥劑的併用劑可以在1個製劑中將兩成分配合之配合劑形態投予，亦可各別作成藥劑投予的形態。各別作成製劑投予時包含同時投予及時間差投予。以時間差投予可先投予本發明化合物，再投予其他藥劑，亦可先投予其他藥劑再投予本發明化合物。各別的投予方法可相同亦可不同。 The combination of the compound of the present invention and another agent may be administered in the form of a combination of the two components in one preparation, or may be separately administered in the form of a pharmaceutical agent. The separate preparations for administration include simultaneous administration and time difference administration. The compound of the present invention may be administered first by administration of a time difference, and other agents may be administered, and other agents may be administered first and then administered to the compound of the present invention. The individual methods of administration may be the same or different.

經由上述併用劑顯示預防及/或治療效果的疾病並無特別限制，只要是將本發明化合物之預防及/或治療效果補齊及/ 或增強的疾病即可。 The disease exhibiting the preventive and/or therapeutic effect by the above-mentioned concomitant is not particularly limited as long as the prophylactic and/or therapeutic effects of the compound of the present invention are complemented and/or Or an enhanced disease can be.

作為補齊及/或增強本發明化合物對於疼痛之預防及/或治療效果之其他藥劑，可列舉例如乙醯胺基酚(acetaminophen)、非類固醇性抗炎症藥、鴉片類藥、抗憂鬱藥、抗癲癇藥、N-甲基-D-天冬胺酸拮抗藥、肌肉鬆弛藥、抗心律不整藥、類固醇藥及雙磷酸鹽藥等。 As other agents which complement and/or enhance the preventive and/or therapeutic effect of the compound of the present invention on pain, for example, acetaminophen , non-steroidal anti-inflammatory drugs, opiates, antidepressants, Antiepileptic drugs, N-methyl-D-aspartic acid antagonists, muscle relaxants, antiarrhythmic drugs, steroid drugs and bisphosphonates.

非類固醇系抗炎症藥可列舉例如雙水楊酸酯(sasapyrine)、水楊酸鈉、阿斯匹林(aspirin)、阿斯匹林.二鋁酸酯配合等阿斯匹林製劑、二氟苯水楊酸(diflunisal)、吲哚美辛(indomethacin)、舒洛芬(suprofen)、烏芬那酯(ufenamate)、二甲基異丙基薁、丁苯羥酸(bufexamac)、聯苯乙酸(felbinac)、待克菲那(diclofenac)、托美汀鈉(tolmetin sodium)、奇諾力(clinoril)、芬布芬(fenbufen)、萘布美酮(nabumetone)、丙谷美辛(proglumetacin)、吲哚美辛法呢酯(indomethacin farnesyl)、阿西美辛(acemetacin)、丙谷美辛馬來酸酯、胺芬酸鈉(amfenac sodium)、莫苯唑酸(mofezolac)、依托度酸(etodolac)、布洛芬(ibuprofen)、布洛芬吡啶甲醇(ibuprofen piconol)、那普洛仙(naproxen)、氟比洛芬(flurbiprofen)、氟比洛芬酯(flurbiprofen axetil)、酮洛芬(ketoprofen)、菲諾洛芬鈣(fenoprofen calcium)、噻洛芬(tiaprofen)、奧沙普(oxaprozin)、普拉諾洛芬(pranoprofen)、洛索洛芬鈉(loxoprofens sodium)、阿明諾洛芬(alminoprofen)、扎托洛芬(zaltoprofen)、甲芬那酸(mefenamic acid)、甲芬那酸鋁(mefenamic acid aluminum)、托芬那酸(tolfenamic acid)、夫洛非寧(floctafenine)、酮基保泰松(ketophenylbutazone)、羥基保泰松(oxyphenbutazone)、匹洛昔康(piroxicam)、特諾昔康 (tenoxicam)、安匹洛昔康(ampiroxicam)、那吧格魯(Napageln)軟膏、依匹唑(epirizole)、鹽酸噻拉米特(tiaramide hydrochloride)、鹽酸替諾立定(tinoridine hydrochloride)、依莫法宗(emorfazone)、蘇爾匹林(sulpyrin)、米格來寧(migrenin)、散利痛(Saridon)、協德斯G(Sedes G)、阿米匹羅-N(amipylo-N)、索魯朋(Sorbon)、匹林系感冒藥、對乙醯胺基酚(acetaminophen)、非那西丁(phenacetin)、甲磺二甲替(dimetotiazine mesilate)、美洛昔康(meloxicam)、塞來可昔布(celecoxib)、羅菲可昔布(rofecoxib)、伐迪可昔布(valdecoxib)、西美曲特(simetride)配合劑及非匹林系感冒藥等。 Examples of the non-steroidal anti-inflammatory drug include aspirin preparations such as sasapyrine, sodium salicylate, aspirin, aspirin, and dialuminate, and difluoro Diflunisal, indomethacin, suprofen, ufenamate , dimethylisopropyl hydrazine , bufexamac, biphenylacetic acid (f Elbinac ), dicofenac, tolmetin sodium , c linoril , fenbufen, nabumetone, proglumetacin ), indomethacin farnesyl , a cemetacin , propargalin maleate , amfenac sodium, moxazol (m ofezolac) , Etodolac, ibuprofen, ibuprofen piconol, naproxen, flurbiprofen, flurbiprofen axetil, Ketoprofen, fenoprofen calcium, tiaprofen, oxaprofen (o xaprozin), Plano, ketoprofen (p ranoprofen), loxoprofen sodium (loxoprofens sodium),阿明诺洛芬(alminoprofen), Zaltoprofen (zaltoprofen), mefenamic acid (m efenamic acid ), mefenamic acid aluminum , tolfenamic acid , f loctafenine , ketophenylbutazone, oxyphenbutazone, meloxicam (as piroxicam), Teno oxicams (tenoxicam), Ann horses meloxicam (ampiroxicam), that it Grew (Napageln) ointment, epinastine oxazole (e pirizole), thiophene hydrochloride La Mite (tiaramide hydrochloride) , tinoridine hydrochloride, e morfazone , sulpyrin, migrenin, saridon, sedes G ), amitylo-N (amipylo-N), sorbon (Sorbon), lysine cold medicine, acetaminophen, phenacetin, metformin (dimetotiazine mesilate), meloxicam, celecoxib, rofecoxib, valdecoxib, simetride, and Non-pilinal cold medicine, etc.

鴉片類藥可列舉例如可待因(codeine)、吩坦尼(fentanyl)、氫嗎啡酮(hydromorphone)、左啡諾(levorphanol)、哌替啶(meperidine)、美沙酮(methadone)、嗎啡(morphine)、羥考酮(oxycodone)、羥嗎啡酮(oxymorphone)及丙氧芬(propoxyphene)等。 The opiate may, for example, be codeine, fentanyl , hydromorphone, levorphanol, meperidine, methadone, morphine. Oxycodone, oxymorphone, and propoxyphene.

抗憂鬱藥可列舉例如三環系抗憂鬱藥(例如鹽酸阿米替林(amitriptyline HCl)、鹽酸米帕明(imipramine HCl)、鹽酸氯米帕明(clomipramine HCl)、鹽酸度硫平(dosulepin HCl)、鹽酸去甲替林(nortriptyline HCl)、鹽酸洛非帕明(lofepramine HCl)、馬來酸曲米帕明(trimipramine maleate)、阿莫沙平(amoxapine)等))、四環系抗憂鬱藥(例如鹽酸馬普替林(maprotiline HCl)、鹽酸米安色林(mianserin HCl)、馬來酸司普替林(setiptiline maleate)等)、單胺氧化酶(MAO)抑制劑(鹽酸沙夫(safrazine HCl)、血清素(serotonin)及正腎上腺素(noradrenaline)再回收抑制劑(SNRI)(例如鹽酸米那普侖(milnacipran HCl)、鹽酸文拉法辛(venlafaxine HCl)等)、選擇性血清素再回收抑制劑(SSRI)(例如馬來酸氟伏沙明(fluvoxamine maleate)、鹽酸帕羅西汀.(paroxetine HCl)、鹽酸氟西汀(fluoxetine HCl)、鹽酸西他羅普蘭(citalopram HCl等)及血清素再回收抑制劑(例如鹽酸曲唑酮(trazodone HCl等)等。 The antidepressant may, for example, be a tricyclic antidepressant (for example, a mitriptyline HCl , imipramine HCl , clomipramine HCl , or sulphur hydrochloride ) Dosulepin HCl ), nortriptyline HCl , lofepramine HCl , tri mipramine maleate , amoxapine, etc. An antidepressant (eg, maprotiline HCl, m ianserin HCl , s etiptiline maleate, etc. ), monoamine oxidase (MAO) inhibitor (hydrochloric acid) Shaf (safrazine HCl), serotonin (serotonin) and norepinephrine (noradrenaline) reuptake inhibitors (SNRIs) (e.g. milnacipran hydrochloride (milnacipran HCl), venlafaxine hydrochloride (venlafaxine HCl), etc.), selective Serotonin Recycling Inhibitor (SSRI) (eg, fluvoxamine maleate, paroxetine HCl , fluoxetine HCl , citalopram hydrochloride (citalopram) HCl or the like and serotonin re-recovery inhibitor (for example, trazodone hydrochloride, etc.).

抗癲癇藥可列舉例如苯巴比妥(Phenobarbital)、普利德敏(puridomin)、苯妥英(phenytoin)、乙琥胺(ethosuximide)、唑尼沙胺(zonisamide)、硝基安定(nitrazepam)、氯硝西泮(clonazepam)、卡巴吖呯(carbamazepine)、丙戊酸鈉(sodium valproate)、乙醯偶氮胺(acetazolamide)及磺斯安(Sulthiame)等。 The antiepileptic drug may, for example, be Phenobarbital, puridomin, phenytoin, ethosuximide, zonisamide, n itrazepam , Clonazepam, carbamazepine, sodium valproate , acetazolamide, and Sulthiame .

N-甲基-D-天冬胺酸拮抗藥可列舉例如鹽酸愷他命(ketamine HCl)、鹽酸金剛烷胺(amantadine HCl)、鹽酸美金剛(memantine HCl)、右旋美沙酚(dextromethorphan)、美沙冬(methadone)等。 The N-methyl-D-aspartic acid antagonist may, for example, be ketamine HCl, amantadine HCl, memantine HCl , or dextromethorphan (d extromethorphan). ) , Meshadong (methadone ), etc.

肌肉鬆弛藥可列舉例如琥珀醯膽鹼(succinylcholine)、丁二醯膽鹼(suxamethonium)、維庫溴銨(vecuronium bromide)、班庫溴銨(pancuronium bromide)及丹曲林鈉(dantrolene Sodium)等。 Muscle relaxants include acyl such as succinic choline (s uccinylcholine), succinic acyl choline (suxamethonium), vecuronium (vecuronium bromide), class libraries bromide (pancuronium bromide) and dantrolene sodium (d antrolene Sodium )etc .

抗心律不整藥可列舉例如普魯卡因胺(procainamide)、雙異丙吡胺(disopyramide)、西苯唑啉(cibenzoline)、吡哌醇(pirmenol)、利多卡因(lidocaine)、美西律(mexiletine)、安搏律定(aprindine)、吡西卡尼(pilsicainide)、氟卡尼(flecainide)、普羅帕酮(propafenone)、普萘洛爾(propranolol)、阿替洛爾(atenolol)、比索洛爾(bisoprolol)、胺碘酮(amiodarone)、索他洛爾(sotalol)、維拉帕米(verapamil)、迪太贊(diltiazem)及苄普地爾(bepridil)等。 Antiarrhythmic drugs include, for example, procainamide, disopyramide, cibenzoline, pirmenol, lidocaine, and mexiletine. (mexiletine), Ann law given stroke (aprindine), topiramate Xi Kani (pilsicainide), flecainide (flecainide), propafenone (p ropafenone), propranolol (p ropranolol), atenolol (atenolol ), bisoprolol (b isoprolol), amiodarone (a miodarone), sotalol (of IV sotalol), verapamil (verapamil), too like Di (of diltiazem) and bepridil (b epridil), etc. .

類固醇藥作為外用藥可列舉例如氯倍他松丙酸酯(clobetasol propionate)、雙氟拉松乙酸酯(diflorasone diacetate)、氟 欣諾能(fluocinonide)、莫米松糠酸酯(mometasone furoate)、倍他米松二丙酸酯(betamethasone dipropionate)、倍他米松丁酸丙酸酯(betamethasone butyrate propionate)、倍他米松戊酸酯(betamethasone valerate)、二氟潑尼酯(difluprednate)、布地奈德(budesonide)、二氟可托龍戊酸酯(diflucortolone valerate)、安席奈德(amcinonide)、哈西奈德(halcinonide)、地塞米松(dexamethasone)、地塞米松丙酸酯(dexamethasone propionate)、地塞米松戊酸酯(dexamethasone valerate)、地塞米松乙酸酯(dexamethasone acetate)、氫化可的松乙酸酯(hydrocortisone acetate)、氫化可的松丁酸酯(hydrocortisone butyrate)、氫化可的松丁酸丙酸酯(hydrocortisone butyrate propionate)、德普羅酮丙酸酯(deprodone propionate)、潑尼松龍戊酸乙酸酯(prednisolone valerate acetate)、氟新龍縮丙酮(fluocinolone acetonide)、貝可米松丙酸酯(beclomethasone propionate)、去炎松縮丙酮(triamcinolone acetonide)、氟米松新戊酸酯(flumethasone pivalate)、阿克美他松丙酸酯(alclomethasone propionate)、氯貝松丁酸酯(clobethasone butyrate)、潑尼松龍(prednisolone)、倍氯米松丙酸酯(peclomethasone propionate)及氟羥可泰(fludroxycortide)等。 Steroids for external use include, for example, as clobetasone propionate (clobetasol propionate), diflorasone acetate (d iflorasone diacetate), can fluoro Agostino (f luocinonide), mometasone furoate (mometasone furoate ), betamethasone dipropionate, betamethasone butyrate propionate, betamethasone valerate, difluprednate, budesonide Budesonide, diflucortolone valerate, amcinonide, h alcinonide , dexamethasone, dexamethasone propionate ), dexamethasone valerate, dexamethasone acetate, hydrocortisone acetate , hydrocortisone butyrate , hydrogenation acid butyrate propionate (hydrocortisone butyrate propionate), De Puluo keto propionate (deprodone propionate), prednisolone acetate valerate (prednisolone valerate acetate), New Dragon-fluoro-acetonide (f luocinolone acetonide), beclomethasone propionate becquerels (beclomethasone propionate), triamcinolone acetonide (triamcinolone acetonide), flumethasone pivalate (flumethasone pivalate), he loose Acme Alclomethasone propionate, clobethasone butyrate, prednisolone, peclomethasone propionate, and fludroxycortide.

作為內服藥或注射藥可列舉可的松乙酸酯(cortisone acetate)、氫化可的松(hydrocortisone)、氫化可的松磷酸鈉(hydrocortisone sodium phosphate)、氫化可的松琥珀酸鈉(hydrocortisone sodium succinate)、氟化可的松乙酸酯(fludrocortisone acetate)、潑尼松龍(prednisolone)、潑尼松龍乙酸酯(prednisolone acetate)、潑尼松龍琥珀酸鈉(prednisolone sodium succinate)、普賴蘇濃丁基乙酸酯(prednisolone butyl acetate)、潑尼松龍磷酸鈉 (prednisolone sodium phosphate)、鹵尼松乙酸酯(halopredone acetate)、甲基潑尼松龍(methylprednisolone)、甲基潑尼松龍乙酸酯(methylprednisolone acetate)、甲基潑尼松龍琥珀酸鈉(methylprednisolone sodium succinate)、去炎松(triamcinolone)、去炎松乙酸酯(triamcinolone acetate)、去炎松縮丙酮(triamcinolone acetonide)、地塞米松(dexamethasone)、地塞米松乙酸酯(dexamethasone acetate)、地塞米松磷酸鈉(dexamethasone sodium phosphate)、地塞米松棕櫚酸酯(dexamethasone palmitate)、對米甲松乙酸酯(paramethasone acetate)及倍他米松(betamethasone)等。 Examples of the internal medicine or the injectable drug include cortisone acetate, hydrocortisone, hydrocortisone sodium phosphate, and hydrocortisone sodium succinate. ), fludrocortisone acetate, prednisolone, prednisolone acetate, prednisolone sodium succinate, puri Prednisolone butyl acetate, prednisolone sodium phosphate (prednisolone sodium phosphate), halopedone acetate, methylprednisolone, methylprednisolone acetate, methylprednisolone sodium succinate (methylprednisolone sodium succinate), triamcinolone, triamcinolone acetate, triamcinolone acetonide, dexamethasone, dexamethasone acetate ), dexamethasone sodium phosphate, dexamethasone palmitate, paramethasone acetate, and betamethasone.

作為吸入藥可列舉貝可米松丙酸酯(beclomethasone propionate)、氟替卡松丙酸酯(fluticasone propionate)、布地奈德(budesonide)、氟尼縮松(flunisolide)、去炎松(triamcinolone)、ST-126P、環索奈德(ciclesonide)、地塞米松棕櫚酸酯(dexamethasone palmitate)、目米松呋喃碳酸酯(momethasone flurane carbonate)、磺酸普拉睪酮(prasterone sulfonate)、地夫可特(deflazacort)、甲基潑尼松龍丁酸酯(methylprednisolone slebutanate)及甲基潑尼松龍琥珀酸鈉等。 Examples of the inhalation drug include beclomethasone propionate, fluticasone propionate, budesonide, flunisolide, triamcinolone, and ST-126P. , ciclesonide (c iclesonide), dexamethasone palmitate (dexamethasone palmitate), flumethasone mesh furyl carbonate (momethasone flurane carbonate), a sulfonic acid Pula testosterone (prasterone sulfonate), deflazacort (d eflazacort) , methylprednisolone slebutanate (methylprednisolone slebutanate) and methylprednisolone sodium succinate.

雙磷酸鹽藥可列舉例如依替膦酸鹽(etidronate)、帕米膦酸鹽(pamidronate)、阿侖膦酸鹽(alendronate)、利塞膦酸鹽(risedronate)、唑來磷酸鹽(zoledronate)及米諾磷酸鹽(minodronate)等。 Bisphosphonate drugs include, for example, etidronate (e tidronate), pamidronate (pamidronate), alendronate (a lendronate), risedronate (r isedronate), zoledronate phosphate (zoledronate) and minophosphonate (m inodronate) .

本發明化合物與其他藥劑之質量比並無特別限制。 The mass ratio of the compound of the present invention to other agents is not particularly limited.

亦可將任意2種以上之其他藥劑組合投予。 Any two or more other pharmaceutical agents may be administered in combination.

又，補齊及/或增強本發明化合物的預防及/或治療效 果之其他藥劑中，根據上述作用機轉，不僅限於至今所發現者，亦包含今後發現者。 Further, to complement and/or enhance the prophylactic and/or therapeutic effect of the compounds of the invention Among other medicines, the above-mentioned action is not limited to those found so far, and includes future discoverers.

以上述之目的使用本發明化合物或本發明化合物與其他藥劑之併用劑，通常以全身性或局部性，、經口或非經口之形態投予。 For the above purposes, the compound of the present invention or a combination of the compound of the present invention and another agent is usually administered in a systemic or topical form, orally or parenterally.

投予量依年齡、體重、症狀、治療效果、投予方法、處理時間等而異，通常，成人每人每次在1mg至1000mg之範圍，以一日一次至數次經口投予，或成人每人每次在0.1mg至100mg之範圍，以一日一次至數次非經口投予，或一日在1小時至24小時之範圍靜脈內持續投予。 The dosage varies depending on the age, body weight, symptoms, therapeutic effect, administration method, treatment time, etc. Usually, each adult is administered orally in the range of 1 mg to 1000 mg once a day to several times a day, or Adults each time in the range of 0.1 mg to 100 mg, administered once or several times a day, or continuously intravenously in the range of 1 hour to 24 hours a day.

如上所述，由於投予量依種種條件而改變，有比上述投予量少之量即足夠的情況，亦有需要投予超過範圍量的情況。 As described above, since the amount of administration varies depending on various conditions, it is sufficient that the amount of the administration is smaller than the above-described dosage, and it is necessary to apply the amount exceeding the range.

投予本發明之化合物、或本發明化合物與其他藥劑的併用劑時，可作為經口投予之內服用固形劑或內服用液劑、及非經口投予之注射劑、外用劑、栓劑、點眼劑、吸入劑等使用。 When the compound of the present invention or a combination of the compound of the present invention and another agent is administered, it can be administered as a solid or internal liquid for oral administration, and an injection, an external preparation or a suppository for parenteral administration. Eye drops, inhalants, etc. are used.

經口投予之內服用固形劑包含錠劑、丸劑、膠囊劑、散劑、顆粒劑等。膠囊劑包含硬膠囊及軟膠囊。又，錠劑包含舌下錠、口腔內貼付錠、口腔內速崩解錠等。 The solid dosage agent for oral administration includes a tablet, a pill, a capsule, a powder, a granule, and the like. Capsules include hard and soft capsules. Further, the tablet contains a sublingual tablet, an in-oral patch, an orally disintegrating tablet or the like.

於該等內服用固形劑中，一種或一種以上之活性物質可為原狀，亦可與賦形劑(乳糖、甘露糖醇、葡萄糖、微結晶纖維素、澱粉等)、結合劑(羥丙基纖維素、聚乙烯吡咯啶酮、偏矽酸鋁酸鎂等)、崩解劑(纖維素乙二酸鈣等)、潤滑劑(硬脂酸鎂等)、安定劑、溶解輔助劑(麩胺酸、天冬胺酸等)等混合，根據常法製 劑化使用。又，視需要可以包覆劑(白糖、明膠、羥丙基纖維素、羥丙基甲基纖維素苯二甲酸酯等)包覆，亦可包覆2層以上。另，亦包含如明膠之可被吸收物質之膠囊。 Among the internal solid dosage agents, one or more active substances may be used as they are, or may be combined with excipients (lactose, mannitol, glucose, microcrystalline cellulose, starch, etc.), binding agents (hydroxypropyl groups). Cellulose, polyvinylpyrrolidone, magnesium metasilicate aluminate, etc., disintegrant (calcium oxalate, etc.), lubricant (magnesium stearate, etc.), stabilizer, dissolution aid (glutamine) Mixed with acid, aspartic acid, etc., according to common law Formulated for use. Further, it may be coated with a coating agent (white sugar, gelatin, hydroxypropylcellulose, hydroxypropylmethylcellulose phthalate or the like) as needed, or may be coated in two or more layers. In addition, capsules such as gelatin which can be absorbed are also included.

經口投予的內服用液劑包含藥劑上容許的水劑、懸濁劑、乳劑、糖漿劑、酏劑等。於該等液劑中，一種或一種以上之活性物質溶解、懸濁或乳化於通常使用之稀釋劑(精製水、乙醇或該等之混合液等)。另，該液劑亦可含有濕潤劑、懸濁化劑、乳化劑、甜味劑、風味劑、芳香劑、保存劑、緩衝劑等。 The orally administered liquid preparation for oral administration contains a water agent, a suspension, an emulsion, a syrup, an expectorant, and the like which are acceptable for the drug. In the liquid preparations, one or more active substances are dissolved, suspended or emulsified in a commonly used diluent (refined water, ethanol or a mixture thereof). Further, the liquid preparation may contain a wetting agent, a suspending agent, an emulsifier, a sweetener, a flavor, a fragrance, a preservative, a buffer, and the like.

非經口投予之外用劑之劑型包含例如軟膏劑、凝膠劑、乳膏劑、濕布劑、貼布劑、塗抹劑、噴霧劑、吸入劑、噴劑、氣溶膠劑、點眼劑及點鼻劑等。該等含有一種或一種以上之活性物質，根據公知之方法或通常使用之處方調劑。 The dosage form for parenteral administration includes, for example, an ointment, a gel, a cream, a wet cloth, a patch, a spread, a spray, an inhalant, a spray, an aerosol, an eye drop, and Point nose and so on. These contain one or more active substances, which are adjusted according to known methods or where they are usually used.

噴霧劑、吸入劑及噴劑除了通常使用之稀釋劑以外，亦可含有如亞硫酸氫鈉之安定劑及賦予等張性之緩衝劑，例如如氯化鈉、檸檬酸鈉或檸檬酸之等張劑。噴劑之製造方法詳細記載於例如美國專利第2，868，691號及美國專利第3，095，355號中。 Sprays, inhalants and sprays may contain, in addition to the diluents normally used, stabilizers such as sodium bisulfite and buffers which impart isotonicity, for example, such as sodium chloride, sodium citrate or citric acid. . The method of producing a spray is described in detail in, for example, U.S. Patent No. 2,868,691 and U.S. Patent No. 3,095,355.

作為非經口投予之注射劑包含溶液、懸濁液、乳濁液及用時溶解或懸濁於溶劑之固體注射劑。注射劑為將一種或一種以上之活性物質溶解、懸濁或乳化於溶劑中使用。溶劑使用例如注射用蒸餾水、生理食鹽水、植物油、丙二醇、聚乙二醇、如乙醇之醇類等及該等之組合。另，該注射劑亦可含有安定劑、溶解輔助劑(麩胺酸、天冬胺酸、聚山梨酸酯80(註冊商標)等)、懸濁化劑、乳化劑、無痛化劑、緩衝劑、保存劑等。該等於最後步驟 進行滅菌或經由無菌操作法製造。又，可製造無菌之固體劑，例如凍結乾燥品，在使用前無菌化、或溶解於無菌注射用蒸餾水或其他溶劑使用。 The injection for parenteral administration contains a solution, a suspension, an emulsion, and a solid injection which is dissolved or suspended in a solvent. The injection is used by dissolving, suspending or emulsifying one or more active substances in a solvent. As the solvent, for example, distilled water for injection, physiological saline, vegetable oil, propylene glycol, polyethylene glycol, an alcohol such as ethanol, or the like, and a combination thereof are used. Further, the injection may contain a stabilizer, a dissolution aid (glutamic acid, aspartic acid, polysorbate 80 (registered trademark), etc.), a suspending agent, an emulsifier, a painless agent, a buffer, Preservatives, etc. This is equal to the last step Sterilize or manufacture via aseptic processing. Further, a sterile solid preparation such as a freeze-dried product can be produced, sterilized before use, or dissolved in sterile distilled water for injection or other solvent.

作為非經口投予之其他組成物包含含有一種或一種以上之活性物質，經由常法處方之直腸投予之栓劑及陰道內投予之子宮帽托等。 Other compositions for parenteral administration include suppositories which are administered by rectal administration, which are one or more active substances, and vaginal caps which are administered intravaginally.

又，本說明書中記載之文獻係引用自參照。 Further, the documents described in the present specification are cited from the reference.

實施例 Example

以下，根據實施例對本發明作詳細的敍述，惟，本發明不限於該等例。 Hereinafter, the present invention will be described in detail based on examples, but the present invention is not limited to the examples.

根據層析法分離處及TLC中表示之括弧內的溶劑係表示使用之溶出溶劑或展開溶劑，比率表示體積比。 The solvent in the parentheses indicated by the chromatographic separation and TLC indicates the elution solvent or developing solvent used, and the ratio indicates the volume ratio.

NMR處表示之括弧內之溶劑係表示測定時使用之溶劑。 The solvent in the brackets indicated by NMR indicates the solvent used in the measurement.

UPLC-MS/ELSD以下述條件實施。 UPLC-MS/ELSD was carried out under the following conditions.

管柱：Waters ACQUITY C18(粒徑：1.7x10-6m；管柱長：30x2.1mm I.D.)；流速：1.0mL/分鐘；管柱温度：40℃；移動相(A)：0.1%三氟乙酸水溶液；移動相(B)：0.1%三氟乙酸-乙腈溶液；梯度(記載移動相(A)：移動相(B)之比率)：[0分]95：5；[0.1分]95：5；[1.2分]5：95；[1.4分]5：95；[1.41分]95：5；[1.5分]95：5；檢測器：UV(PDA)、ELSD、MS。 Column: Waters ACQUITY C 18 (particle size: 1.7x10 -6 m; column length: 30x2.1mm ID); flow rate: 1.0mL/min; column temperature: 40°C; mobile phase (A): 0.1% Aqueous solution of fluoroacetic acid; mobile phase (B): 0.1% trifluoroacetic acid-acetonitrile solution; gradient (recording mobile phase (A): ratio of mobile phase (B)): [0 points] 95:5; [0.1 minutes] 95 :5; [1.2 points] 5:95; [1.4 points] 5:95; [1.41 points] 95:5; [1.5 points] 95:5; detectors: UV (PDA), ELSD, MS.

本說明書中使用之化合物名稱通常使用以IUPAC之 規則為基準命名之電腦程式、或是使用ACD/Name(註冊商標)或Chemdraw Ultra(版本12.0、Cambridge Soft公司製造)命名者。 The names of the compounds used in this specification are usually used in IUPAC. The program is a computer program named after the standard, or is named after ACD/Name (registered trademark) or Chemdraw Ultra (version 12.0, manufactured by Cambridge Soft).

實施例1：5-溴-N-(5-溴噻唑-2-基)戊醯胺 Example 1: 5-Bromo-N-(5-bromothiazol-2-yl)pentanamide

於5-溴噻唑-2-胺溴酸鹽(1g)之二氯甲烷(12mL)溶液中加入吡啶(0.68mL)及5-溴戊醯氯(0.54mL)之二氯甲烷(0.7mL)溶液。將反應混合物於室溫攪拌2小時。於反應混合物中加入甲醇(0.7mL)，減壓下進行濃縮。於獲得之殘渣中加入1N鹽酸(13mL)。將獲得之固體以第三丁基甲醚洗淨後乾燥，獲得具有以下物性值之標題化合物(1.06g)。 A solution of pyridine (0.68 mL) and 5-bromopentyl chloride (0.54 mL) in dichloromethane (0.7 mL) was added to a solution of 5-bromothiazole-2-amine bronic acid (1 g) in dichloromethane (12 mL) . The reaction mixture was stirred at room temperature for 2 hours. Methanol (0.7 mL) was added to the reaction mixture, and concentrated under reduced pressure. 1N Hydrochloric acid (13 mL) was added to the obtained residue. The obtained solid was washed with tributyl methyl ether and dried to give the title compound (1.06 g).

TLC：Rf 0.50(己烷：乙酸乙酯=3：1)。 TLC: Rf 0.50 (hexane: ethyl acetate = 3:1).

實施例2：1-(5-溴噻唑-2-基)哌啶-2-酮 Example 2: 1-(5-Bromothiazol-2-yl)piperidin-2-one

於實施例1製造之化合物(1.06g)之二甲基甲醯胺(3.5mL)溶液中，於冰冷下加入碳酸鉀(860mg)。反應混合物於室溫攪拌5小時。於反應混合物中加入水(60mL)，攪拌17小時。析出之固體以水(14mL)洗淨後乾燥，獲得具有以下物性值之標題化合物(830mg)。 To a solution of the compound (1.06 g) in dimethylformamide (3.5 mL). The reaction mixture was stirred at room temperature for 5 hours. Water (60 mL) was added to the reaction mixture and stirred for 17 hr. The precipitated solid was washed with water (14 mL) and dried to give the title compound ( 830 mg).

TLC：Rf 0.53(己烷：乙酸乙酯=3：1)。 TLC: Rf 0.53 (hexane: ethyl acetate = 3:1).

實施例3：1-(5-(4-羥基苯基)噻唑-2-基)哌啶-2-酮 Example 3: 1-(5-(4-Hydroxyphenyl)thiazol-2-yl)piperidin-2-one

於氬氣環境下將實施例2製造之化合物(700mg)溶解於四氫呋喃及1，4-二烷之混合溶液(1：1，14mL)中。於反應混合物中加入(4-羥基苯基)硼酸(440mg)、四-三苯基膦鈀(150mg)、磷酸三鉀水溶液(2mol/L，2.7mL)，於90℃攪拌2小時。於反應混合物中加入水，濾取析出之固體。獲得之固體以甲醇洗淨後乾燥，獲得具有以下物性值之標題化合物(511mg)。 The compound (700 mg) produced in Example 2 was dissolved in tetrahydrofuran and 1,4-two under an argon atmosphere. A mixture of alkane (1:1, 14 mL). (4-Hydroxyphenyl)boronic acid (440 mg), tetrakistriphenylphosphine palladium (150 mg), and an aqueous solution of tripotassium phosphate (2 mol/L, 2.7 mL) were added to the reaction mixture, and the mixture was stirred at 90 ° C for 2 hours. Water was added to the reaction mixture, and the precipitated solid was collected by filtration. The obtained solid was washed with methanol and dried to give the title compound (511 mg).

TLC：Rf 0.38(己烷：乙酸乙酯=1：1)。 TLC: Rf 0.38 (hexane: ethyl acetate = 1:1).

實施例4：1-(5-(4-((5-硝基嘧啶-2-基)氧基)苯基)噻唑-2-基)哌啶-2-酮 Example 4: 1-(5-(4-((5-Nitropyrimidin-2-yl)oxy)phenyl)thiazol-2-yl)piperidin-2-one

將氫化鈉(81mg)懸濁於二甲基甲醯胺(1.3mL)。將該溶液於0℃冷卻。於該溶液中加入實施例3製造之化合物(530mg)之二甲基甲醯胺(3.3mL)溶液。將反應混合物攪拌30分鐘，加入2-氯-5-硝基嘧啶之二甲基甲醯胺(0.7mL)溶液，攪拌15分鐘。於反應混合物中加入水，濾取析出之固體並，乾燥，獲得具有以下物性值之標題化合物(698mg)。 Sodium hydride (81 mg) was suspended in dimethylformamide (1.3 mL). The solution was cooled at 0 °C. A solution of the compound (530 mg) produced in Example 3 in dimethylformamide (3.3 mL) was added. The reaction mixture was stirred for 30 minutes, a solution of 2-chloro-5-nitropyrimidine in dimethylformamide (0.7 mL) was added and stirred for 15 min. Water was added to the reaction mixture, and the precipitated solid was filtered and dried to give the title compound (698 mg).

TLC：Rf 0.42(己烷：乙酸乙酯=1：1)。 TLC: Rf 0.42 (hexane: ethyl acetate = 1:1).

實施例5：1-(5-(4-((5-胺基嘧啶-2-基)氧基)苯基)噻唑-2-基)哌啶-2-酮 Example 5: 1-(5-(4-((5-Aminopyrimidin-2-yl)oxy)phenyl)thiazol-2-yl)piperidin-2-one

將鋅(380mg)懸濁於水(1.9mL)，加入氯化銨(310mg)及實施例4製造之化合物(580mg)之二甲基甲醯胺(5.8mL)溶液，於室溫攪拌4小時。於反應混合物中加入水，以Celite(註冊商標)過濾後以乙酸乙酯萃取濾液。獲得之有機層以無水硫酸鈉乾燥後於減壓下進行濃縮，獲得具有以下物性值之標題化合物(280mg)。 Zinc (380 mg) was suspended in water (1.9 mL), and a solution of ammonium chloride (310 mg) and the compound of Example 4 (580 mg) in dimethylformamide (5.8 mL) was added and stirred at room temperature for 4 hours. . Water was added to the reaction mixture, and the mixture was filtered through Celite (registered trademark), and the filtrate was extracted with ethyl acetate. The obtained organic layer was dried over anhydrous sodium sulfate and evaporated.

TLC：Rf 0.21(己烷：乙酸乙酯=1：4)。 TLC: Rf 0.21 (hexane: ethyl acetate = 1 : 4).

實施例6：3-硝基-5，6’-雙(三氟甲基)-2，3’-二吡啶 Example 6: 3-Nitro-5,6'-bis(trifluoromethyl)-2,3'-dipyridine

於氬氣環境下，於2-氯-3-硝基-5-(三氟甲基)吡啶(1g)之1，4-二烷(15mL)溶液中加入(6-(三氟甲基)吡啶-3-基)硼酸(925mg)、三環己基膦之15%甲苯溶液(2.0mL)、三(二亞苄基丙酮)二鈀(2.02g)、磷酸三鉀水溶液(2mol/L，5.9mL)，於90℃攪拌整晚。於反應混合物中加入水，以Celite(註冊商標)過濾後以乙酸乙酯萃取濾液。獲得之有機層以無水硫酸鈉乾燥後減壓下進行濃縮。獲得之殘渣以 矽膠管柱層析儀(己烷：乙酸乙酯=85：15)分離精製，獲得具有以下物性值之標題化合物(1.15g)。 1,4-Bis in 2-chloro-3-nitro-5-(trifluoromethyl)pyridine (1g) under argon A solution of (6-(trifluoromethyl)pyridin-3-yl)boronic acid (925 mg), a 15% toluene solution of tricyclohexylphosphine (2.0 mL), and tris(dibenzylideneacetone) were added to a solution of alkane (15 mL). Palladium (2.02 g) and an aqueous solution of tripotassium phosphate (2 mol/L, 5.9 mL) were stirred at 90 ° C overnight. Water was added to the reaction mixture, and the mixture was filtered through Celite (registered trademark), and the filtrate was extracted with ethyl acetate. The obtained organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue obtained was separated and purified by a silica gel column chromatography (hexane: ethyl acetate = 85: 15) to give the title compound (1.15 g).

TLC：Rf 0.34(己烷：乙酸乙酯=9：1)。 TLC: Rf 0.34 (hexane: ethyl acetate = 9:1).

實施例7：5，6’-雙(三氟甲基)-[2，3’-二吡啶]-3-胺 Example 7: 5,6'-bis(trifluoromethyl)-[2,3'-dipyridine]-3-amine

使用實施例6製造之化合物替代實施例4製造之化合物，進行與實施例5相同之操作，獲得具有以下物性值之標題化合物。 The compound produced in Example 6 was used in place of the compound produced in Example 4, and the same operation as in Example 5 was carried out to obtain the title compound.

TLC：Rf 0.31(己烷：乙酸乙酯=4：1)。 TLC: Rf 0.31 (hexane: ethyl acetate = 4:1).

實施例8：2，2，2-三氯乙基(5，6’-雙(三氟甲基)-[2，3’-二吡啶]-3-基)胺基甲酸酯 Example 8: 2,2,2-trichloroethyl (5,6'-bis(trifluoromethyl)-[2,3'-dipyridyl]-3-yl)carbamate

於實施例7製造之化合物(863mg)之四氫呋喃(9.4mL)溶液中加入碳酸氫鈉(708mg)、氯甲酸2，2，2-三氯乙酯(378μL)，攪拌整晚。於反應混合物中加入水，以乙酸乙酯萃取。獲得之有機層以飽和食鹽水洗淨，以無水硫酸鈉乾燥後減壓下進行濃縮。獲得之殘渣以矽膠層析儀(己烷：乙酸乙酯=9：1)分離精製，獲得具有以下物性值之標題化合物(1.15g)。 To a solution of the compound (863 mg) obtained in Example 7 in THF (yield: 9.4 EtOAc), EtOAc (EtOAc) Water was added to the reaction mixture, and extracted with ethyl acetate. The obtained organic layer was washed with brine, dried over anhydrous sodium sulfate and evaporated. The residue obtained was separated and purified by silica gel chromatography (hexane: ethyl acetate = 9:1) to give the title compound (1.15 g).

TLC：Rf 0.53(己烷：乙酸乙酯=4：1)。 TLC: Rf 0.53 (hexane: ethyl acetate = 4:1).

實施例9：1-[5，6’-雙(三氟甲基)-2，3’-二吡啶-3-基]-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 9: 1-[5,6'-bis(trifluoromethyl)-2,3'-dipyridin-3-yl]-3-(2-{4-[2-(2- oxooxy) -1-piperidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

於實施例8製造之化合物(170mg)之二甲亞碸(1.2mL) 溶液中加入實施例5製造之化合物(120mg)、1-甲基吡咯啶(10μL)，於80℃攪拌整晚。反應混合物以矽膠管柱層析儀(二氯甲烷：乙酸乙酯=1：1)分離精製，獲得具有以下物性值之本發明化合物(77.5mg)。 Methyl hydrazine (1.2 mL) of the compound (170 mg) produced in Example 8. The compound (120 mg) and 1-methylpyrrolidine (10 μL) produced in Example 5 were added to the solution, and stirred at 80 ° C overnight. The reaction mixture was separated and purified using a silica gel column chromatography (dichloromethane: ethyl acetate = 1:1) to give the compound of the present invention (77.5 mg).

TLC：Rf 0.36(己烷：乙酸乙酯=1：4)； 1H-NMR(DMSO-d6)：δ 1.82-1.99(m，4 H)，2.61(t，2 H)，4.07(t，2 H)，7.22(d，2 H)，7.66(d，2 H)，7.91(s，1 H)，8.10(d，1 H)，8.38-8.41(m，1 H)，8.67-8.82(m，5 H)，9.05(s，1 H)，9.24(s，1 H)。 TLC: Rf 0.36 (hexane: ethyl acetate = 1 : 4); 1 H-NMR (DMSO-d 6 ): δ 1.82-1.99 (m, 4 H), 2.61 (t, 2 H), 4.07 (t) , 2 H), 7.22 (d, 2 H), 7.66 (d, 2 H), 7.91 (s, 1 H), 8.10 (d, 1 H), 8.38-8.41 (m, 1 H), 8.67-8.82 (m, 5 H), 9.05 (s, 1 H), 9.24 (s, 1 H).

實施例10：噻唑-2-基胺基甲酸第三丁酯 Example 10: T-butyl thiazol-2-ylaminocarbamate

於噻唑-2-胺(200mg)之N-甲基吡咯啶酮(2.3mL)溶液中加入二碳酸二-第三丁酯(480mg)，將反應混合物於室溫攪拌17小時。於反應混合物中加入水(10mL)，濾取析出之固體。將該固體洗淨後乾燥，獲得具有以下物性值之標題化合物(390mg)。 To a solution of thiazolidine-2-amine (200 mg) in N-methylpyrrolidone (2.3 mL) was added EtOAc. Water (10 mL) was added to the reaction mixture, and the precipitated solid was filtered. The solid was washed and dried to give the title compound (390 mg).

TLC：Rf 0.52(己烷：乙酸乙酯=4：1)。 TLC: Rf 0.52 (hexane: ethyl acetate = 4:1).

實施例11：乙基(噻唑-2-基)胺基甲酸第三丁酯 Example 11: tert-butyl ethyl (thiazol-2-yl)carbamate

於實施例10製造之化合物(200mg)之N-甲基吡咯啶酮(1mL)溶液中加入磷酸三鉀(212mg)及碘乙烷(172mg)。反應混合物於室溫攪拌17小時。於反應混合物中加入水(15mL)，以第三丁基甲醚(15mL)萃取。獲得之有機層以飽和食鹽水洗淨，以無水硫酸鈉乾燥後減壓下進行濃縮，獲得具有以下物性值之標題化合物(211mg)。 To a solution of the compound (200 mg) of N-methylpyrrolidone (1 mL) obtained in Example 10, was added tribasic phosphate (212 mg) and ethyl iodide (172 mg). The reaction mixture was stirred at room temperature for 17 hours. Water (15 mL) was added to the mixture and the mixture was evaporated. The obtained organic layer was washed with brine, dried over anhydrous sodium sulfate

TLC：Rf 0.69(己烷：乙酸乙酯=4：1)。 TLC: Rf 0.69 (hexane: ethyl acetate = 4:1).

實施例12：2-(4-溴苯氧基)-5-硝基嘧啶 Example 12: 2-(4-Bromophenoxy)-5-nitropyrimidine

於4-溴苯酚(200mg)之四氫呋喃溶液中加入三乙胺(193μL)及2-氯-5-硝基嘧啶(204mg)。反應混合物於室溫攪拌3小時。將反應混合物加入水(20mL)中，以乙酸乙酯(20mL)萃取。獲得之有機層以飽和食鹽水洗淨，以無水硫酸鈉乾燥後減壓下進行濃縮，獲得具有以下物性值之標題化合物(294mg)。 Triethylamine (193 μL) and 2-chloro-5-nitropyrimidine (204 mg) were added to a solution of 4-bromophenol (200 mg) in tetrahydrofuran. The reaction mixture was stirred at room temperature for 3 hours. The reaction mixture was poured into EtOAc (20 mL). The obtained organic layer was washed with brine, dried over anhydrous sodium sulfate

TLC：Rf 0.44(己烷：乙酸乙酯=4：1)。 TLC: Rf 0.44 (hexane: ethyl acetate = 4:1).

實施例13：2-(4-溴苯氧基)嘧啶-5-胺 Example 13: 2-(4-Bromophenoxy)pyrimidine-5-amine

於氬氣環境下，於2-(4-溴苯氧基)-5-硝基嘧啶(400mg)之四氫呋喃(20mL)/甲醇(20mL)溶液中加入3%白金-碳(200mg)。將該反應混合物於氫氣環境下，於室溫攪拌3小時。反應混合物以Celite(註冊商標)過濾，獲得具有以下物性值之標題化合物(363mg)。 To a solution of 2-(4-bromophenoxy)-5-nitropyrimidine (400 mg) in tetrahydrofuran (20 mL) / methanol (20 mL) The reaction mixture was stirred at room temperature for 3 hours under a hydrogen atmosphere. The reaction mixture was filtered through Celite (registered trademark) to give the title compound (363 mg).

TLC：Rf 0.33(己烷：乙酸乙酯=1：1)。 TLC: Rf 0.33 (hexane: ethyl acetate = 1:1).

實施例14：第三丁基(5-(4-((5-胺基嘧啶-2-基)氧基)苯基)噻唑-2-基)(乙基)胺基甲酸酯 Example 14: Ternyl butyl (5-(4-((5-aminopyrimidin-2-yl)oxy)phenyl)thiazol-2-yl)(ethyl)carbamate

於氬氣環境下，於2-(4-溴苯氧基)嘧啶-5-胺(233mg)之二甲基乙醯胺(3mL)溶液中加入實施例11製造之化合物(1g)、三甲基乙酸(54mg)、碳酸鉀(363mg)及三環己基鏻四氟硼酸酯(64mg)。於反應混合物中加入乙酸鈀(20mg)。以微波將反應混合物於120℃攪拌1小時。反應混合物以矽膠管柱層析儀(己烷：乙酸乙酯=1：2)分離精製，獲得具有以下物性值之標題化合物(173mg)。 The compound (1 g) produced in Example 11 was added to a solution of 2-(4-bromophenoxy)pyrimidine-5-amine (233 mg) in dimethylacetamide (3 mL) under argon. Acetic acid (54 mg), potassium carbonate (363 mg) and tricyclohexyl fluorene tetrafluoroborate (64 mg). Palladium acetate (20 mg) was added to the reaction mixture. The reaction mixture was stirred at 120 ° C for 1 hour with microwave. The reaction mixture was separated and purified by silica gel column chromatography (hexane: ethyl acetate = 1:1) to give the title compound (173 mg).

TLC：Rf 0.51(己烷：乙酸乙酯=4：1)。 TLC: Rf 0.51 (hexane: ethyl acetate = 4:1).

實施例15：1-[5，6’-雙(三氟甲基)-2，3’-二吡啶-3-基]-3-(2-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 15: 1-[5,6'-bis(trifluoromethyl)-2,3'-dipyridin-3-yl]-3-(2-{4-[2-(ethylamino)- 1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

於使用實施例14製造之化合物替代實施例5製造之化合物而，進行與實施例9相同之操作獲得之化合物(138mg)之二氯甲烷(1.8mL)溶液中加入三氟乙酸(0.4mL)。反應混合物於室溫攪拌6小時。於反應混合物中加入飽和碳酸氫鈉水溶液，以乙酸乙酯萃取。獲得之有機層以飽和食鹽水洗淨。獲得之有機層以無水硫酸鈉乾燥後減壓下進行濃縮。獲得之殘渣以二氯甲烷洗淨，獲得具有以下物性值之本發明化合物(96mg)。 Trifluoroacetic acid (0.4 mL) was added to a solution of the compound (138 mg) obtained from m. The reaction mixture was stirred at room temperature for 6 hours. A saturated aqueous solution of sodium hydrogencarbonate was added and the mixture was evaporated. The obtained organic layer was washed with saturated brine. The obtained organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue obtained was washed with dichloromethane to give a compound (96 mg) of the present invention.

TLC：Rf 0.22(乙酸乙酯：己烷=1：1)；1H-NMR(DMSO-d6)：δ 1.16(t，3 H)，3.26(m，2 H)，7.13(d，2 H)，7.43-7.46(m，3 H)，7.72(t，1 H)，8.11(d，1 H)，8.40(dd，1 H)，8.66(s，2 H)，8.72(s，1 H)，8.79(d，1 H)，8.83(d，1 H)，9.06(d，1 H)，9.23(s，1 H)。 TLC: Rf 0.22 (ethyl acetate:hexane = 1:1); 1 H-NMR (DMSO-d 6 ): δ 1.16 (t, 3 H), 3.26 (m, 2 H), 7.13 (d, 2) H), 7.43-7.46 (m, 3 H), 7.72 (t, 1 H), 8.11 (d, 1 H), 8.40 (dd, 1 H), 8.66 (s, 2 H), 8.72 (s, 1) H), 8.79 (d, 1 H), 8.83 (d, 1 H), 9.06 (d, 1 H), 9.23 (s, 1 H).

實施例16：2，2，2-三氯乙基(2-(3，4-二甲基苯基)-5-(三氟甲基)吡啶-3-基)胺基甲酸酯 Example 16: 2,2,2-Trichloroethyl(2-(3,4-dimethylphenyl)-5-(trifluoromethyl)pyridin-3-yl)carbamate

使用(3，4-二甲基苯基)硼酸替代(6-(三氟甲基)吡啶-3-基)硼酸，進行與實施例6→實施例5→實施例8相同之操作，獲得具有以下物性值之標題化合物。 Using (3,4-dimethylphenyl)boronic acid instead of (6-(trifluoromethyl)pyridin-3-yl)boronic acid, the same operation as in Example 6→Example 5→Example 8 was carried out to obtain The title compound of the following physical properties.

TLC：Rf 0.62(己烷：乙酸乙酯=4：1)。 TLC: Rf 0.62 (hexane: ethyl acetate = 4:1).

實施例17：1-[2-(3，4-二甲基苯基)-5-(三氟甲基)-3-吡啶 基]-3-(2-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 17: 1-[2-(3,4-Dimethylphenyl)-5-(trifluoromethyl)-3-pyridine 3-(2-{4-[2-(ethylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

使用實施例16製造之化合物替代實施例8製造之化合物，進行與實施例9→實施例15相同之操作，獲得具有以下物性值之本發明化合物。 Using the compound produced in Example 16 in place of the compound produced in Example 8, the same operation as in Example 9 → Example 15 was carried out to obtain a compound of the present invention having the following physical property.

TLC：Rf 0.23(乙酸乙酯：己烷=1：1)；1H-NMR(DMSO-d6)：δ 1.16(t，3 H)，2.30(s，3 H)，2.30(s，3 H)，3.26(m，2 H)，7.13(d，2 H)，7.3O-7.46(m，6 H)，7.72(t，1 H)，8.34(s，1 H)，8.66(s，2 H)，8.66(s，1 H)，8.78(s，1 H)，9.50(s，1 H)。 TLC: Rf 0.23 (ethyl acetate:hexane = 1:1); 1 H-NMR (DMSO-d 6 ): δ 1.16 (t, 3 H), 2.30 (s, 3 H), 2.30 (s, 3) H), 3.26 (m, 2 H), 7.13 (d, 2 H), 7.3O-7.46 (m, 6 H), 7.72 (t, 1 H), 8.34 (s, 1 H), 8.66 (s, 2 H), 8.66 (s, 1 H), 8.78 (s, 1 H), 9.50 (s, 1 H).

實施例18：(5-溴噻唑-2-基)(異丙基)胺基甲酸第三丁酯 Example 18: (5-Bromothiazol-2-yl)(isopropyl)carbamic acid tert-butyl ester

使用2-碘丙烷替代碘乙烷，進行與實施例11相同之操作，獲得具有以下物性值之標題化合物。 The same procedure as in Example 11 was carried out using 2-iodopropane instead of ethyl iodide to give the title compound.

TLC：Rf 0.59(己烷：乙酸乙酯=9：1)。 TLC: Rf 0.59 (hexane: ethyl acetate = 9:1).

實施例19：1-(2-(4-溴苯氧基)嘧啶-5-基)-3-(2-(3，4-二甲基苯基)-5-(三氟甲基)吡啶-3-基)脲 Example 19: 1-(2-(4-Bromophenoxy)pyrimidin-5-yl)-3-(2-(3,4-dimethylphenyl)-5-(trifluoromethyl)pyridine -3-yl)urea

使用實施例16製造之化合物替代實施例8製造之化合物，使用實施例13製造之化合物替代實施例7製造之化合物，進行與實施例9相同之操作，獲得具有以下物性值之標題化合物。 The compound produced in Example 16 was used in place of the compound produced in Example 8, and the compound produced in Example 13 was used in place of the compound produced in Example 7, and the same procedure as in Example 9 was carried out to obtain the title compound having the following property.

TLC：Rf 0.35(己烷：乙酸乙酯=1：1)。 TLC: Rf 0.35 (hexane: ethyl acetate = 1:1).

實施例20：1-(2-(3，4-二甲基苯基)-5-(三氟甲基)吡啶-3-基)-3-(2-(4-(4，4，5，5-四甲基-1，3，2-二硼烷-2-基)苯氧基)嘧啶-5-基)脲 Example 20: 1-(2-(3,4-Dimethylphenyl)-5-(trifluoromethyl)pyridin-3-yl)-3-(2-(4-(4,4,5) ,5-tetramethyl-1,3,2-di Borane-2-yl)phenoxy)pyrimidin-5-yl)urea

於氬氣環境下，於實施例19製造之化合物(270mg)之二甲亞碸(1.6mL)溶液中加入雙(聯頻哪醇)硼酸酯(160mg)、乙酸鉀(240mg) 及1，1’-雙(二苯基膦基)二茂鐵-二氯化鈀(II)-二氯甲烷錯合物(20mg)，於80℃攪拌3小時。於反應混合物中加入水，以Celite(註冊商標)過濾，以乙酸乙酯萃取濾液。獲得之有機層以水洗淨，以無水硫酸鈉乾燥後減壓下進行濃縮。獲得之殘渣以乙酸乙酯洗淨，獲得具有以下物性值之標題化合物(213mg)。 To a solution of the compound (270 mg) in dimethyl hydrazine (1.6 mL) obtained in Example 19 under argon, bis(dipinacol) borate (160 mg), potassium acetate (240 mg) And 1,1'-bis(diphenylphosphino)ferrocene-palladium(II) chloride-dichloromethane complex (20 mg) was stirred at 80 ° C for 3 hours. Water was added to the reaction mixture, which was filtered over Celite (registered trademark), and the filtrate was extracted with ethyl acetate. The obtained organic layer was washed with water, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The obtained residue was washed with ethyl acetate to give the title compound (213 mg).

TLC：Rf 0.40(氯仿：乙酸乙酯=9：1)。 TLC: Rf 0.40 (chloroform: ethyl acetate = 9:1).

實施例21：1-[2-(3，4-二甲基苯基)-5-(三氟甲基)-3-吡啶基]-3-(2-{4-[2-(異丙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 21:1-[2-(3,4-Dimethylphenyl)-5-(trifluoromethyl)-3-pyridyl]-3-(2-{4-[2-(isopropylamine) -1,3-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

於氬氣環境下，於實施例20製造之化合物(200mg)之1，4-二烷(1.1mL)溶液中加入實施例18製造之化合物(127mg)、四-三苯基膦鈀(19mg)及磷酸三鉀水溶液(2mol/L，660μL)，於80℃攪拌1.5小時。於反應混合物中加入水，以乙酸乙酯萃取。獲得之有機層以飽和食鹽水洗淨，以無水硫酸鈉乾燥後減壓下進行濃縮。獲得之殘渣以矽膠管柱層析儀(己烷：乙酸乙酯=1：1)分離精製，獲得第三丁基(5-(4-((5-(3-(2-(3，4-二甲基苯基)-5-(三氟甲基)吡啶-3-基)脲基)嘧啶-2-基)氧基)苯基)噻唑-2-基)(異丙基)胺基甲酸酯(134mg)。於該胺基甲酸酯化合物(134mg)之二氯甲烷(2mL)溶液中加入三氟乙酸(2mL)，攪拌1.5小時。於飽和碳酸氫鈉水溶液中加入反應混合物，濾取析出之固體。獲得之固體以水及乙酸乙酯洗淨後乾燥，獲得具有以下物性值之本發明化合物(41.3mg)。 1,4-two of the compound (200 mg) produced in Example 20 under an argon atmosphere A compound (127 mg), tetra-triphenylphosphine palladium (19 mg) and a tripotassium phosphate aqueous solution (2 mol/L, 660 μL) were added to a solution of alkane (1.1 mL), and stirred at 80 ° C for 1.5 hours. Water was added to the reaction mixture, and extracted with ethyl acetate. The obtained organic layer was washed with brine, dried over anhydrous sodium sulfate and evaporated. The residue obtained was separated and purified by a ruthenium column chromatography (hexane: ethyl acetate = 1:1) to obtain a tributyl group (5-(4-((5-(3-(2-(3)) -Dimethylphenyl)-5-(trifluoromethyl)pyridin-3-yl)ureido)pyrimidin-2-yl)oxy)phenyl)thiazol-2-yl)(isopropyl)amino Formate (134 mg). Trifluoroacetic acid (2 mL) was added to a solution of the carbamic acid compound (134 mg) in dichloromethane (2 mL) and stirred for 1.5 hr. The reaction mixture was added to a saturated aqueous solution of sodium hydrogencarbonate, and the precipitated solid was collected by filtration. The obtained solid was washed with water and ethyl acetate, and dried to give the compound (41.3 mg) of the present invention.

TLC：Rf 0.27(己烷：乙酸乙酯=1：1)；1H-NMR(DMSO-d6)：δ 1.18(d，6 H)，2.31(s，6 H)，3.80(m，1 H)，7.13(d，2 H)，7.30-7.45(m，6 H)，7.64(d，1 H)，8.34(s，1 H)，8.66(s，2 H)，8.68(s，1 H)，8.78(s，1 H)，9.50(s，1 H)。 TLC: Rf 0.27 (hexane: ethyl acetate = 1:1); 1 H-NMR (DMSO-d 6 ): δ 1.18 (d, 6 H), 2.31 (s, 6 H), 3.80 (m, 1) H), 7.13 (d, 2 H), 7.30-7.45 (m, 6 H), 7.64 (d, 1 H), 8.34 (s, 1 H), 8.66 (s, 2 H), 8.68 (s, 1) H), 8.78 (s, 1 H), 9.50 (s, 1 H).

實施例22：2，2，2-三氯乙基(2-(對-甲苯基)-5-(三氟甲基)吡啶-3-基)胺基甲酸酯 Example 22: 2,2,2-trichloroethyl(2-(p-tolyl)-5-(trifluoromethyl)pyridin-3-yl)carbamate

使用(4-甲基苯基)硼酸替代(6-(三氟甲基)吡啶-3-基)硼酸，進行與實施例6→實施例5→實施例8相同之操作，獲得具有以下物性值之標題化合物。 The same operation as in Example 6 → Example 5 → Example 8 was carried out by using (4-methylphenyl)boronic acid instead of (6-(trifluoromethyl)pyridin-3-yl)boronic acid to obtain the following physical property. The title compound.

TLC：Rf 0.61(己烷：乙酸乙酯=4：1)。 TLC: Rf 0.61 (hexane: ethyl acetate = 4:1).

實施例23：1-(2-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-(4-甲基苯基)-5-(三氟甲基)-3-吡啶基]脲 Example 23: 1-(2-{4-[2-(ethylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-[2-(4- Methylphenyl)-5-(trifluoromethyl)-3-pyridyl]urea

使用實施例22製造之化合物替代實施例8製造之化合物，進行與實施例9→實施例15相同之操作，獲得具有以下物性值之本發明化合物。 Using the compound produced in Example 22 in place of the compound produced in Example 8, the same operation as in Example 9 - Example 15 was carried out to obtain a compound of the present invention having the following physical properties.

TLC：Rf 0.49(己烷：乙酸乙酯=1：4)；1H-NMR(DMSO-d6)：δ 1.17(t，3 H)，2.40(s，3 H)，3.25(m，2 H)，7.13(d，2 H)，7.37(d，2 H)，7.43-7.47(m，3 H)，7.54(d，2 H)，7.72(t，1 H)，8.37(s，1 H)，8.65(s，2 H)，8.68(s，1 H)，8.75(s，1 H)，9.46(s，1 H)。 TLC: Rf 0.49 (hexane: ethyl acetate = 1 : 4); 1 H-NMR (DMSO-d 6 ): δ 1.17 (t, 3 H), 2.40 (s, 3 H), 3.25 (m, 2) H), 7.13 (d, 2 H), 7.37 (d, 2 H), 7.43-7.47 (m, 3 H), 7.54 (d, 2 H), 7.72 (t, 1 H), 8.37 (s, 1) H), 8.65 (s, 2 H), 8.68 (s, 1 H), 8.75 (s, 1 H), 9.46 (s, 1 H).

實施例24：2，2，2-三氯乙基(2-苯基-5-(三氟甲基)吡啶-3-基)胺基甲酸酯 Example 24: 2,2,2-trichloroethyl(2-phenyl-5-(trifluoromethyl)pyridin-3-yl)carbamate

使用苯基硼酸替代(6-(三氟甲基)吡啶-3-基)硼酸，進行與實施例6→實施例5→實施例8相同之操作，獲得具有以下物性值之標題化合物。 The same procedure as in Example 6 → Example 5 → Example 8 was carried out using phenylboronic acid instead of (6-(trifluoromethyl)pyridin-3-yl)boronic acid to give the title compound.

TLC：Rf 0.64(己烷：乙酸乙酯=4：1)。 TLC: Rf 0.64 (hexane: ethyl acetate = 4:1).

實施例25：1-(2-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-苯基-5-(三氟甲基)-3-吡啶基]脲 Example 25: 1-(2-{4-[2-(ethylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-[2-phenyl- 5-(trifluoromethyl)-3-pyridyl]urea

使用實施例24製造之化合物替代實施例8製造之化合物，進行與實施例9→實施例15相同之操作，獲得具有以下物性值之本發明化合物。 The compound produced in Example 24 was used in place of the compound produced in Example 8, and the same procedures as in Example 9 - Example 15 were carried out to obtain a compound of the present invention having the following property values.

TLC：Rf 0.27(己烷：乙酸乙酯=1：1)；1H-NMR(DMSO-d6)：δ 1.16(t，3 H)，3.25(m，2 H)，7.12(d，2 H)，7.42-7.45(m，3 H)，7.52-7.58(m，3 H)，7.64-7.66(m，2 H)，7.71(t，1 H)，8.41(s，1 H)，8.65(s，2 H)，8.72(s，1 H)，8.75(s，1 H)，9.44(s，1 H)。 TLC: Rf 0.27 (hexane: ethyl acetate = 1:1); 1 H-NMR (DMSO-d 6 ): δ 1.16 (t, 3 H), 3.25 (m, 2 H), 7.12 (d, 2) H), 7.42-7.45 (m, 3 H), 7.52-7.58 (m, 3 H), 7.64-7.66 (m, 2 H), 7.71 (t, 1 H), 8.41 (s, 1 H), 8.65 (s, 2 H), 8.72 (s, 1 H), 8.75 (s, 1 H), 9.44 (s, 1 H).

實施例26：2，2，2-三氯乙基(2-(間-甲苯基)-5-(三氟甲基)吡啶-3-基)胺基甲酸酯 Example 26: 2,2,2-trichloroethyl(2-(m-tolyl)-5-(trifluoromethyl)pyridin-3-yl)carbamate

使用間-甲苯基硼酸替代(6-(三氟甲基)吡啶-3-基)硼酸，進行與實施例6→實施例5→實施例8相同之操作，獲得具有以下物性值之標題化合物。 The same procedure as in Example 6 → Example 5 → Example 8 was carried out using m-tolylboronic acid instead of (6-(trifluoromethyl)pyridin-3-yl)boronic acid to give the title compound.

TLC：Rf 0.64(己烷：乙酸乙酯=4：1)。 TLC: Rf 0.64 (hexane: ethyl acetate = 4:1).

實施例27：1-(2-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-(3-甲基苯基)-5-(三氟甲基)-3-吡啶基]脲 Example 27: 1-(2-{4-[2-(ethylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-[2-(3- Methylphenyl)-5-(trifluoromethyl)-3-pyridyl]urea

使用實施例26製造之化合物替代實施例8製造之化合物，進行與實施例9→實施例15相同之操作，獲得具有以下物性值之本發明化合物。 Using the compound produced in Example 26 in place of the compound produced in Example 8, the same operation as in Example 9 - Example 15 was carried out to obtain a compound of the present invention having the following physical property.

TLC：Rf 0.45(己烷：乙酸乙酯=1：1)；1H-NMR(DMSO-d6)：δ 1.16(t，3 H)，2.40(s，3 H)，3.25(m，2 H)，7.12(d，2 H)，7.33-7.45(m，7 H)，7.71(t，1 H)，8.36(s，1 H)，8.64(s，2 H)，8.69(s，1 H)，8.76(s，1 H)，9.48(s，1 H)。 TLC: Rf 0.45 (hexane: ethyl acetate = 1:1); 1 H-NMR (DMSO-d 6 ): δ 1.16 (t, 3 H), 2.40 (s, 3 H), 3.25 (m, 2) H), 7.12 (d, 2 H), 7.33-7.45 (m, 7 H), 7.71 (t, 1 H), 8.36 (s, 1 H), 8.64 (s, 2 H), 8.69 (s, 1) H), 8.76 (s, 1 H), 9.48 (s, 1 H).

實施例28：5-(4-((5-胺基嘧啶-2-基)氧基)苯基)-N-(第三丁 基)噻唑-2-胺 Example 28: 5-(4-((5-Aminopyrimidin-2-yl)oxy)phenyl)-N-(Third Thiazol-2-amine

使用N-(第三丁基)噻唑-2-胺替代實施例11製造之化合物，進行與實施例14相同之操作，獲得具有以下物性值之標題化合物。TLC：Rf 0.33(己烷：乙酸乙酯=1：2)。 The compound produced in Example 11 was replaced with N-(t-butyl)thiazole-2-amine, and the same procedure as in Example 14 was carried out to obtain the title compound. TLC: Rf 0.33 (hexane: ethyl acetate = 1:2).

實施例29：1-[2-(3，4-二甲基苯基)-5-(三氟甲基)-3-吡啶基]-3-[2-(4-{2-[(2-甲基-2-丙基)胺基]-1，3-噻唑-5-基}苯氧基)-5-嘧啶基]脲 Example 29: 1-[2-(3,4-Dimethylphenyl)-5-(trifluoromethyl)-3-pyridyl]-3-[2-(4-{2-[(2) -Methyl-2-propyl)amino]-1,3-thiazol-5-yl}phenoxy)-5-pyrimidinyl]urea

使用實施例28製造之化合物替代實施例5製造之化合物，使用實施例16製造之化合物替代實施例8製造之化合物，進行與實施例9相同之操作，獲得具有以下物性值之本發明化合物。 The compound produced in Example 28 was used in place of the compound produced in Example 5, and the compound produced in Example 16 was used in place of the compound produced in Example 8, and the same operation as in Example 9 was carried out to obtain a compound of the present invention having the following property values.

TLC：Rf 0.60(己烷：乙酸乙酯=1：2)；1H-NMR(DMSO-d6)：δ 1.37(s，9 H)，2.31(s，6 H)，7.12(dd，2 H)，7.30-7.43(m，6 H)，7.49(s，1 H)，8.33(s，1 H)，8.65(s，2 H)，8.67(s，1 H)，8.77(dd，1 H)，9.49(s，1 H)。 TLC: Rf 0.60 (hexane: ethyl acetate = 1:2); 1 H-NMR (DMSO-d 6 ): δ 1.37 (s, 9 H), 2.31 (s, 6 H), 7.12 (dd, 2) H), 7.30-7.43 (m, 6 H), 7.49 (s, 1 H), 8.33 (s, 1 H), 8.65 (s, 2 H), 8.67 (s, 1 H), 8.77 (dd, 1) H), 9.49 (s, 1 H).

實施例30：第三丁基(5-溴噻唑-2-基)(乙基)胺基甲酸酯 Example 30: Ternyl butyl (5-bromothiazol-2-yl)(ethyl) urethane

使用5-溴噻唑-2-胺氫溴酸鹽替代噻唑-2-胺，進行與實施例10→實施例11相同之操作，獲得具有以下物性值之標題化合物。 The same procedure as in Example 10 → Example 11 was carried out using 5-bromothiazole-2-amine hydrobromide instead of thiazole-2-amine to give the title compound.

TLC：Rf 0.45(己烷：乙酸乙酯=19：1)。 TLC: Rf 0.45 (hexane: ethyl acetate = 19:1).

實施例31：第三丁基乙基(5-(4-羥基苯基)噻唑-2-基)胺基甲酸酯 Example 31: Third butylethyl (5-(4-hydroxyphenyl)thiazol-2-yl)carbamate

於氬氣環境下，將實施例30製造之化合物(280mg)溶解於四氫呋喃與乙醇之混合溶液(1：1，3mL)中。於該溶液中加入(4-羥基苯基)硼酸(140mg)、四-三苯基膦鈀(53mg)及磷酸三鉀水溶液(2mol/L，140mL)，於75℃攪拌3小時。於反應混合物中追加(4- 羥基苯基)硼酸(12mg)及四-三苯基膦鈀(21mg)，另攪拌1.5小時。於反應混合物中加入飽和氯化銨水溶液，以乙酸乙酯萃取。獲得之有機層以飽和食鹽水洗淨，以無水硫酸鈉乾燥後減壓下進行濃縮。獲得之殘渣以矽膠管柱層析儀(己烷：乙酸乙酯=9：1→3：1)分離精製，獲得具有以下物性值之標題化合物(211mg)。 The compound (280 mg) produced in Example 30 was dissolved in a mixed solution of tetrahydrofuran and ethanol (1:1, 3 mL) under an argon atmosphere. To the solution were added (4-hydroxyphenyl)boronic acid (140 mg), tetrakistriphenylphosphine palladium (53 mg), and a solution of tri-potassium phosphate (2 mol/L, 140 mL), and stirred at 75 ° C for 3 hours. Added to the reaction mixture (4- Hydroxyphenyl)boronic acid (12 mg) and tetrakistriphenylphosphine palladium (21 mg) were stirred for an additional 1.5 hours. A saturated aqueous solution of ammonium chloride was added to the mixture, and ethyl acetate was evaporated. The obtained organic layer was washed with brine, dried over anhydrous sodium sulfate and evaporated. The residue obtained was separated and purified by a silica gel column chromatography (hexane: ethyl acetate = 9:1 to 3:1) to give the title compound (211 mg).

TLC：Rf 0.49(己烷：乙酸乙酯=3：1)。 TLC: Rf 0.49 (hexane: ethyl acetate = 3:1).

實施例32：第三丁基乙基(5-(4-((5-硝基吡啶-2-基)氧基)苯基)噻唑-2-基)胺基甲酸酯 Example 32: Third butylethyl (5-(4-((5-nitropyridin-2-yl)oxy)phenyl)thiazol-2-yl)carbamate)

於實施例31製造之化合物(741mg)之二甲基甲醯胺(8mL)溶液中加入2-氯-5-硝基吡啶(385mg)及碳酸鉀(480mg)，於90℃攪拌1.5小時。於反應混合物中加入水，濾取析出之固體，乾燥，獲得具有以下物性值之標題化合物(1.04g)。 2-Chloro-5-nitropyridine (385 mg) and potassium carbonate (480 mg) were added to a solution of the compound (741 mg. Water was added to the reaction mixture, and the precipitated solid was filtered and dried to give the title compound (1.04 g).

TLC：Rf 0.58(己烷：乙酸乙酯=3：1)。 TLC: Rf 0.58 (hexane: ethyl acetate = 3:1).

實施例33：第三丁基(5-(4-((5-胺基吡啶-2-基)氧基)苯基)噻唑-2-基)(乙基)胺基甲酸酯 Example 33: Ternyl butyl (5-(4-((5-aminopyridin-2-yl)oxy)phenyl)thiazol-2-yl)(ethyl)carbamate

使用實施例32製造之化合物替代實施例4製造之化合物，進行與實施例5相同之操作，獲得具有以下物性值之標題化合物。 Using the compound produced in Example 32 in place of the compound produced in Example 4, the same operation as in Example 5 was carried out to obtain the title compound having the following property.

TLC：Rf 0.20(己烷：乙酸乙酯=3：2)。 TLC: Rf 0.20 (hexane: ethyl acetate = 3:2).

實施例34：1-[2-(3，4-二甲基苯基)-5-(三氟甲基)-3-吡啶基]-3-(6-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)脲 Example 34: 1-[2-(3,4-Dimethylphenyl)-5-(trifluoromethyl)-3-pyridyl]-3-(6-{4-[2-(ethylamine) -1,3-1,3-thiazol-5-yl]phenoxy}-3-pyridyl)urea

使用實施例33製造之化合物替代實施例5製造之化合物，使用實施例16製造之化合物替代實施例8製造之化合物，進行與實施例9→實施例15相同之操作，獲得具有以下物性值之本發明化合物。 The compound produced in Example 33 was used in place of the compound produced in Example 5, and the compound produced in Example 16 was used in place of the compound produced in Example 8, and the same operation as in Example 9 → Example 15 was carried out to obtain a material having the following physical properties. Inventive compound.

TLC：Rf 0.47(己烷：乙酸乙酯=1：2)；1H-NMR(DMSO-d6)：δ 1.29(t，3 H)，2.25(s，3 H)，2.26(s，3 H)，3.22-3.37(m，2 H)，5.24(br s，1 H)，6.89(s，1 H)，7.07(s，2 H)，7.13-7.20(m，4 H)，7.23-7.27(m，1 H)，7.39(d，3 H)，7.82-7.95(m，2 H)，8.56(d，1 H)，8.92(d，1 H)。 TLC: Rf 0.47 (hexane: ethyl acetate = 1:2); 1 H-NMR (DMSO-d 6 ): δ 1.29 (t, 3 H), 2.25 (s, 3 H), 2.26 (s, 3) H), 3.22-3.37 (m, 2 H), 5.24 (br s, 1 H), 6.89 (s, 1 H), 7.07 (s, 2 H), 7.13-7.20 (m, 4 H), 7.23 7.27 (m, 1 H), 7.39 (d, 3 H), 7.82 - 7.95 (m, 2 H), 8.56 (d, 1 H), 8.92 (d, 1 H).

實施例35：1-(6-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)-3-[2-苯基-5-(三氟甲基)-3-吡啶基]脲 Example 35: 1-(6-{4-[2-(ethylamino)-1,3-thiazol-5-yl]phenoxy}-3-pyridyl)-3-[2-phenyl- 5-(trifluoromethyl)-3-pyridyl]urea

使用實施例33製造之化合物替代實施例5製造之化合物，使用實施例24製造之化合物替代實施例8製造之化合物，進行與實施例9→實施例15相同之操作，獲得具有以下物性值之本發明化合物。 The compound produced in Example 33 was used in place of the compound produced in Example 5, and the compound produced in Example 24 was used in place of the compound produced in Example 8, and the same operation as in Example 9 → Example 15 was carried out to obtain a material having the following physical properties. Inventive compound.

TLC：Rf 0.29(己烷：乙酸乙酯=1：3)；1H-NMR(CDCl3)：δ 1.31(t，3 H)，3.24-3.40(m，2 H)，5.47(br s，1 H)，6.85-7.00(m，3 H)，7.08(d，2 H)，7.24(s，1 H)，7.42(d，2 H)，7.45-7.53(m，5 H)，7.86(dd，1 H)，7.93(d，1 H)，8.61(s，1 H)，8.94(s，1 H)。 TLC: Rf 0.29 (hexane: ethyl acetate = 1 : 3); 1 H-NMR (CDCl 3 ): δ 1.31 (t, 3 H), 3.24 - 3.40 (m, 2 H), 5.47 (br s, 1 H), 6.85-7.00 (m, 3 H), 7.08 (d, 2 H), 7.24 (s, 1 H), 7.42 (d, 2 H), 7.45-7.53 (m, 5 H), 7.86 ( Dd, 1 H), 7.93 (d, 1 H), 8.61 (s, 1 H), 8.94 (s, 1 H).

實施例36：2，2，2-三氯乙基(2-(3-(羥基甲基)苯基)-5-(三氟甲基)吡啶-3-基)胺基甲酸酯 Example 36: 2,2,2-Trichloroethyl(2-(3-(hydroxymethyl)phenyl)-5-(trifluoromethyl)pyridin-3-yl)carbamate

使用(3-(羥基甲基)苯基)硼酸替代(6-(三氟甲基)吡啶-3-基)硼酸，使用2-氯-5-(三氟甲基)吡啶-3-胺替代2-氯-3-硝基-5-(三氟甲 基)吡啶，進行與實施例6→實施例8相同之操作，獲得具有以下物性值之標題化合物。 Replacement of (6-(trifluoromethyl)pyridin-3-yl)boronic acid with (3-(hydroxymethyl)phenyl)boronic acid using 2-chloro-5-(trifluoromethyl)pyridin-3-amine 2-chloro-3-nitro-5-(trifluoromethyl) The same procedure as in Example 6 → Example 8 was carried out to give the title compound.

TLC：Rf 0.57(己烷：乙酸乙酯=1：1)。 TLC: Rf 0.57 (hexane: ethyl acetate = 1:1).

實施例37：1-(2-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-{2-[3-(羥基甲基)苯基]-5-(三氟甲基)-3-吡啶基}脲 Example 37: 1-(2-{4-[2-(ethylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-{2-[3- (hydroxymethyl)phenyl]-5-(trifluoromethyl)-3-pyridyl}urea

使用實施例36製造之化合物替代實施例8製造之化合物，進行與實施例9→實施例15相同之操作，獲得具有以下物性值之本發明化合物。 The compound produced in Example 36 was used in place of the compound produced in Example 8, and the same operation as in Example 9 - Example 15 was carried out to obtain a compound of the present invention having the following property values.

TLC：Rf 0.45(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 1.16(t，3 H)，3.25(m，2 H)，4.60(d，2 H)，5.30(t，1 H)，7.13(d，2 H)，7.42-7.52(m，6 H)，7.59(s，1 H)，7.72(t，1 H)，8.39(s，1 H)，8.65(s，2 H)，8.71(s，1 H)，8.76(s，1 H)，9.45(s，1 H)。 TLC: Rf 0.45 (ethyl acetate); 1 H-NMR (DMSO -d 6): δ 1.16 (t, 3 H), 3.25 (m, 2 H), 4.60 (d, 2 H), 5.30 (t, 1 H), 7.13 (d, 2 H), 7.42-7.52 (m, 6 H), 7.59 (s, 1 H), 7.72 (t, 1 H), 8.39 (s, 1 H), 8.65 (s, 2 H), 8.71 (s, 1 H), 8.76 (s, 1 H), 9.45 (s, 1 H).

實施例38：2，2，2-三氯乙基(5-(三氟甲基)-[2，3’-二吡啶]-3-基)胺基甲酸酯 Example 38: 2,2,2-trichloroethyl(5-(trifluoromethyl)-[2,3'-dipyridyl]-3-yl)carbamate

使用吡啶-3-基硼酸替代(6-(三氟甲基)吡啶-3-基)硼酸，使用2-氯-5-(三氟甲基)吡啶-3-胺替代2-氯-3-硝基-5-(三氟甲基)吡啶，進行與實施例6→實施例8相同之操作，獲得具有以下物性值之標題化合物。 Substituting pyridine-3-ylboronic acid for (6-(trifluoromethyl)pyridin-3-yl)boronic acid, 2-chloro-5-(trifluoromethyl)pyridin-3-amine for 2-chloro-3- Nitro-5-(trifluoromethyl)pyridine was subjected to the same operation as Example 6 to Example 8 to give the title compound.

TLC：Rf 0.67(乙酸乙酯)。 TLC: Rf 0.67 (EtOAc).

實施例39：1-(2-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[5-(三氟甲基)-2，3’-二吡啶-3-基]脲 Example 39: 1-(2-{4-[2-(ethylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-[5-(trifluoro Methyl)-2,3'-dipyridin-3-yl]urea

使用實施例38製造之化合物替代實施例8製造之化合物，進行與實施例9→實施例15相同之操作，獲得具有以下物性值之本 發明化合物。 The compound produced in Example 38 was used in place of the compound produced in Example 8, and the same operation as in Example 9 → Example 15 was carried out to obtain a material having the following physical properties. Inventive compound.

TLC：Rf 0.60(乙酸乙酯：甲醇=19：1)；1H-NMR(DMSO-d6)：δ 1.16(t，3 H)，3.25(m，2 H)，7.13(d，2 H)，7.42-7.46(m，3 H)，7.59(dd，1 H)，7.17(t，1 H)，8.07-8.09(m，1 H)，8.59(s，1 H)，8.65(s，2 H)，8.72-8.78(m，3 H)，8.85(s，1 H)，9.33(s，1 H)。 TLC: Rf 0.60 (ethyl acetate: methanol = 19: 1); 1 H -NMR (DMSO-d 6): δ 1.16 (t, 3 H), 3.25 (m, 2 H), 7.13 (d, 2 H ), 7.42-7.46 (m, 3 H), 7.59 (dd, 1 H), 7.17 (t, 1 H), 8.07-8.09 (m, 1 H), 8.59 (s, 1 H), 8.65 (s, 2 H), 8.72-8.78 (m, 3 H), 8.85 (s, 1 H), 9.33 (s, 1 H).

實施例40：第三丁基(5-溴噻唑-2-基)(2-乙氧基乙基)胺基甲酸酯 Example 40: Ternyl butyl (5-bromothiazol-2-yl)(2-ethoxyethyl) urethane

使用5-溴噻唑-2-胺氫溴酸鹽替代噻唑-2-胺，使用1-溴-2-乙氧基乙烷替代碘乙烷，進行與實施例10→實施例11相同之操作，獲得具有以下物性值之標題化合物。 The same operation as in Example 10 → Example 11 was carried out by using 5-bromothiazole-2-amine hydrobromide in place of thiazol-2-amine and 1-bromo-2-ethoxyethane in place of iodoethane. The title compound having the following physical property values was obtained.

TLC：Rf 0.44(己烷：乙酸乙酯=3：1)。 TLC: Rf 0.44 (hexane: ethyl acetate = 3:1).

實施例41：1-[2-(3，4-二甲基苯基)-5-(三氟甲基)-3-吡啶基]-3-[2-(4-{2-[(2-乙氧基乙基)胺基]-1，3-噻唑-5-基}苯氧基)-5-嘧啶基]脲 Example 41:1-[2-(3,4-Dimethylphenyl)-5-(trifluoromethyl)-3-pyridyl]-3-[2-(4-{2-[(2) -ethoxyethyl)amino]-1,3-thiazol-5-yl}phenoxy)-5-pyrimidinyl]urea

使用實施例40製造之化合物替代實施例18製造之化合物，進行與實施例21相同之操作，獲得具有以下物性值之本發明化合物。 The compound produced in Example 40 was used in place of the compound produced in Example 18, and the same operation as in Example 21 was carried out to obtain a compound of the present invention having the following property values.

TLC：Rf 0.34(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 1.12(t，3 H)，2.32(s，6 H)，3.40-3.54(m，6 H)，7.13(d，2 H)，7.30-7.63(m，6 H)，7.82(t，1 H)，7.37(s，1 H)，8.62(s，2 H)，8.66(s，1 H)，8.78(s，1 H)，9.50(s，1 H)。 TLC: Rf 0.34 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 1.12 (t, 3 H), 2.32 (s, 6 H), 3.40-3.54 (m, 6 H), 7.13 ( d, 2 H), 7.30-7.63 (m, 6 H), 7.82 (t, 1 H), 7.37 (s, 1 H), 8.62 (s, 2 H), 8.66 (s, 1 H), 8.78 ( s, 1 H), 9.50 (s, 1 H).

實施例42：第三丁基(5-溴噻唑-2-基)(丙基)胺基甲酸酯 Example 42: Ternyl butyl (5-bromothiazol-2-yl) (propyl) urethane

使用5-溴噻唑-2-胺氫溴酸鹽替代噻唑-2-胺，使用1-碘丙烷替 代碘乙烷，進行與實施例10→實施例11相同之操作，獲得具有以下物性值之標題化合物。 Substituting 5-bromothiazole-2-amine hydrobromide for thiazol-2-amine using 1-iodopropane The same procedure as in Example 10 → Example 11 was carried out to give the title compound.

TLC：Rf 0.41(己烷：乙酸乙酯=4：1)。 TLC: Rf 0.41 (hexane: ethyl acetate = 4:1).

實施例43：1-[2-(3，4-二甲基苯基)-5-(三氟甲基)-3-吡啶基]-3-(2-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 43: 1-[2-(3,4-Dimethylphenyl)-5-(trifluoromethyl)-3-pyridyl]-3-(2-{4-[2-(propylamino) )-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

使用實施例42製造之化合物替代實施例18製造之化合物，進行與實施例21相同之操作，獲得具有以下物性值之本發明化合物。 Using the compound produced in Example 42 in place of the compound produced in Example 18, the same operation as in Example 21 was carried out to obtain a compound of the present invention having the following property values.

TLC：Rf 0.55(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 0.91(t，3 H)，1.57(m，2 H)，2.34(s，6 H)，3.18(m，2 H)，7.13(d，2 H)，7.30-7.46(m，6 H)，7.76(t，1 H)，8.34(s，1 H)，8.63(s，2 H)，8.66(s，1 H)，8.77(d，1 H)，9.50(s，1 H)。 TLC: Rf 0.55 (ethyl acetate); 1 H-NMR (DMSO -d 6): δ 0.91 (t, 3 H), 1.57 (m, 2 H), 2.34 (s, 6 H), 3.18 (m, 2 H), 7.13 (d, 2 H), 7.30-7.46 (m, 6 H), 7.76 (t, 1 H), 8.34 (s, 1 H), 8.63 (s, 2 H), 8.66 (s, 1 H), 8.77 (d, 1 H), 9.50 (s, 1 H).

實施例44：2，2，2-三氯乙基(2-(鄰-甲苯基)-5-(三氟甲基)吡啶-3-基)胺基甲酸酯 Example 44: 2,2,2-trichloroethyl(2-(o-tolyl)-5-(trifluoromethyl)pyridin-3-yl)carbamate

使用鄰-甲苯基硼酸替代(6-(三氟甲基)吡啶-3-基)硼酸，進行與實施例6→實施例5→實施例8相同之操作，獲得具有以下物性值之標題化合物。 The same procedure as in Example 6 → Example 5 → Example 8 was carried out using o-tolylboronic acid instead of (6-(trifluoromethyl)pyridin-3-yl)boronic acid to give the title compound.

TLC：Rf 0.67(己烷：乙酸乙酯=4：1)。 TLC: Rf 0.67 (hexane: ethyl acetate = 4:1).

實施例45：1-(2-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-(2-甲基苯基)-5-(三氟甲基)-3-吡啶基]脲 Example 45: 1-(2-{4-[2-(ethylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-[2-(2- Methylphenyl)-5-(trifluoromethyl)-3-pyridyl]urea

使用實施例44製造之化合物替代實施例8製造之化合物，進行與實施例9→實施例15相同之操作，獲得具有以下物性值之本發明化合物。 The compound produced in Example 44 was used in place of the compound produced in Example 8, and the same operation as in Example 9 - Example 15 was carried out to obtain a compound of the present invention having the following property values.

TLC：Rf 0.55(二氯甲烷：乙酸乙酯：甲醇=8：4：1)；1H-NMR(DMSO-d6)：δ 1.16(t，3H)，2.06(s，3H)，3.20-3.30(m，2H)，7.12(d，2H)，7.28(d，1H)，7.34-7.50(m，6H)，7.71(t，1H)，7.97(s，1H)，8.63(s，2H)，8.66-8.70(m，1H)，8.86-8.90(m，1H)，9.50(s，1H)。 TLC: Rf 0.55 (dichloromethane: ethyl acetate: methanol = 8: 4: 1); 1 H-NMR (DMSO-d 6): δ 1.16 (t, 3H), 2.06 (s, 3H), 3.20- 3.30 (m, 2H), 7.12 (d, 2H), 7.28 (d, 1H), 7.34 - 7.50 (m, 6H), 7.71 (t, 1H), 7.97 (s, 1H), 8.63 (s, 2H) , 8.66-8.70 (m, 1H), 8.86-8.90 (m, 1H), 9.50 (s, 1H).

實施例46：3-硝基-2-苯氧基-5-(三氟甲基)吡啶 Example 46: 3-Nitro-2-phenoxy-5-(trifluoromethyl)pyridine

於2-氯-3-硝基-5-(三氟甲基)吡啶(1280mg)之二甲基甲醯胺(18mL)溶液中加入苯酚(800mg)及碳酸銫(5530mg)。反應混合物於60℃攪拌3小時。反應混合物以乙酸乙酯稀釋，以水及飽和食鹽水洗淨。獲得之有機層以無水硫酸鎂乾燥，減壓下進行濃縮。獲得之殘渣以矽膠管柱層析儀(己烷：乙酸乙酯=1：19)精製，獲得具有以下物性值之標題化合物(370mg)。 Phenol (800 mg) and cesium carbonate (5530 mg) were added to a solution of 2-chloro-3-nitro-5-(trifluoromethyl)pyridine (1280 mg) in dimethylformamide (18 mL). The reaction mixture was stirred at 60 ° C for 3 hours. The reaction mixture was diluted with ethyl acetate and washed with water and brine. The organic layer obtained was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue obtained was purified by a silica gel column chromatography (hexane: ethyl acetate: 1:1) to give the title compound (370 mg).

TLC：Rf 0.41(乙酸乙酯：己烷=1：19)。 TLC: Rf 0.41 (ethyl acetate:hexane = 1:19).

實施例47：2，2，2-三氯乙基(2-苯氧基-5-(三氟甲基)吡啶-3-基)胺基甲酸酯 Example 47: 2,2,2-trichloroethyl(2-phenoxy-5-(trifluoromethyl)pyridin-3-yl)carbamate

使用實施例46製造之化合物替代實施例4製造之化合物，進行與實施例5→實施例8相同之操作，獲得具有以下物性值之標題化合物。 The compound produced in Example 46 was used in place of the compound produced in Example 4, and the same procedure as in Example 5 - Example 8 was carried out to obtain the title compound.

TLC：Rf 0.60(乙酸乙酯：己烷=1：9)。 TLC: Rf 0.60 (ethyl acetate:hexane = 1:9).

實施例48：1-(2-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-苯氧基-5-(三氟甲基)-3-吡啶基]脲 Example 48: 1-(2-{4-[2-(ethylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-[2-phenoxy -5-(trifluoromethyl)-3-pyridyl]urea

使用實施例47製造之化合物替代實施例8製造之化合物，進行與實施例9→實施例15相同之操作，獲得具有以下物性值之本發明化合物。 The compound produced in Example 47 was used in place of the compound produced in Example 8, and the same procedures as in Example 9 - Example 15 were carried out to obtain a compound of the present invention having the following property values.

TLC：Rf 0.20(乙酸乙酯：己烷=1：1)；1H-NMR(DMSO-d6)：δ 1.16(t，3 H)，3.21-3.30(m，2 H)，7.13-7.17(m，2 H)，7.24-7.32(m，3 H)，7.43-7.51(m，5 H)，7.72(t，1 H)，8.08-8.12(m，1 H)，8.73(s，2 H)，8.83(d，1 H)，9.20(s，1 H)，9.59(s，1 H)。 TLC: Rf 0.20 (ethyl acetate:hexane = 1:1); 1 H-NMR (DMSO-d 6 ): δ 1.16 (t, 3 H), 3.21-3.30 (m, 2 H), 7.13-7. (m, 2 H), 7.24 - 7.32 (m, 3 H), 7.43 - 7.51 (m, 5 H), 7.72 (t, 1 H), 8.08-8.12 (m, 1 H), 8.73 (s, 2) H), 8.83 (d, 1 H), 9.20 (s, 1 H), 9.59 (s, 1 H).

實施例49：1-(5-(4-((5-胺基嘧啶-2-基)氧基)苯基)噻唑-2-基)吡咯啶-2-酮 Example 49: 1-(5-(4-((5-Aminopyrimidin-2-yl)oxy)phenyl)thiazol-2-yl)pyrrolidin-2-one

使用4-溴丁醯氯替代5-溴戊醯氯，進行與實施例1→實施例2→實施例3→實施例4→實施例5相同之操作，獲得具有以下物性值之標題化合物。 The same procedure as in Example 1 → Example 2 → Example 3 → Example 4 → Example 5 was carried out using 4-bromobutylphosphonium chloride in place of 5-bromopentafluorene chloride to obtain the title compound having the following physical property.

TLC：Rf 0.52(二氯甲烷：乙酸乙酯：甲醇=8：4：1)。 TLC: Rf 0.52 (dichloromethane: ethyl acetate:methanol = 8:4:1).

實施例50：1-[5，6’-雙(三氟甲基)-2，3’-二吡啶-3-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 50: 1-[5,6'-Bis(trifluoromethyl)-2,3'-dipyridin-3-yl]-3-(2-{4-[2-(2-)oxy -1-pyrrolidyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

使用實施例49製造之化合物替代實施例5製造之化合物，進行與實施例9相同之操作，獲得具有以下物性值之本發明化合物。 Using the compound produced in Example 49 in place of the compound produced in Example 5, the same operation as in Example 9 was carried out to obtain a compound of the present invention having the following physical property.

TLC：Rf 0.57(二氯甲烷：乙酸乙酯：甲醇=8：4：1)；1H-NMR(DMSO-d6)：δ 2.10-2.24(m，2 H)，2.63(t，2 H)，4.04(t，2 H)，7.21(d，2 H)，7.66(d，2 H)，7.89(s，1 H)，8.10(d，1 H)，8.36-8.42(m，1 H)，8.66(s，2 H)，8.71(s，1 H)，8.78(s，1 H)，8.82(s，1 H)，9.04(s，1 H)，9.23(s，1 H)。 TLC: Rf 0.57 (dichloromethane: ethyl acetate:methanol = 8:4:1); 1 H-NMR (DMSO-d 6 ): δ 2.10-2.24 (m, 2 H), 2.63 (t, 2 H) ), 4.04 (t, 2 H), 7.21 (d, 2 H), 7.66 (d, 2 H), 7.89 (s, 1 H), 8.10 (d, 1 H), 8.36-8.42 (m, 1 H) ), 8.66 (s, 2 H), 8.71 (s, 1 H), 8.78 (s, 1 H), 8.82 (s, 1 H), 9.04 (s, 1 H), 9.23 (s, 1 H).

實施例50-1：1-[2-(3，4-二甲基苯基)-5-(三氟甲基)-3-吡啶基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 50-1:1-[2-(3,4-Dimethylphenyl)-5-(trifluoromethyl)-3-pyridyl]-3-(2-{4-[2-( 2-sided oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

使用實施例49製造之化合物替代實施例5製造之化合物，使用實施例16製造之化合物替代實施例8製造之化合物，進行與實施例9相同之操作，獲得具有以下物性值之本發明化合物。 The compound produced in Example 49 was used in place of the compound produced in Example 5, and the compound produced in Example 16 was used in place of the compound produced in Example 8, and the same procedure as in Example 9 was carried out to obtain a compound of the present invention having the following property values.

TLC：Rf 0.62(二氯甲烷：乙酸乙酯：甲醇=8：4：1)；1H-NMR(DMSO-d6)：δ 2.10-2.24(m，2 H)，2.31(s，6 H)，2.64(t，2 H)，4.05(t，2 H)，7.22(d，2 H)，7.30-7.38(m，2 H)，7.41(s，1 H)，7.67(d，2 H)，7.90(s，1 H)，8.35(s，1 H)，8.67(s，3 H)，8.77(s，1 H)，9.51(s，1 H)。 TLC: Rf 0.62 (dichloromethane: ethyl acetate:methanol = 8:4:1); 1 H-NMR (DMSO-d 6 ): δ 2.10-2.24 (m, 2 H), 2.31 (s, 6 H) ), 2.64 (t, 2 H), 4.05 (t, 2 H), 7.22 (d, 2 H), 7.30-7.38 (m, 2 H), 7.41 (s, 1 H), 7.67 (d, 2 H) ), 7.90 (s, 1 H), 8.35 (s, 1 H), 8.67 (s, 3 H), 8.77 (s, 1 H), 9.51 (s, 1 H).

實施例51：1-[2-(3，4-二甲基苯基)-5-(三氟甲基)-3-吡啶基]-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 51:1-[2-(3,4-Dimethylphenyl)-5-(trifluoromethyl)-3-pyridyl]-3-(2-{4-[2-(2- Oxo-1-piperidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

使用實施例16製造之化合物替代實施例8製造之化合物，進行與實施例9相同之操作，獲得具有以下物性值之本發明化合物。 Using the compound produced in Example 16 in place of the compound produced in Example 8, the same operation as in Example 9 was carried out to obtain a compound of the present invention having the following physical properties.

TLC：Rf 0.58(二氯甲烷：乙酸乙酯=4：1)；1H-NMR(DMSO-d6)：δ 1.80-2.00(m，4 H)，2.31(s，6 H)，2.61(t，2 H)，4.07(t，2 H)，7.22(d，2 H)，7.30-7.40(m，2 H)，7.41(s，1 H)，7.66(d，2 H)，7.91(s，1 H)，8.35(s，1 H)，8.67(m，3 H)，8.77(s，1 H)，9.51(s，1 H)。 TLC: Rf 0.58 (dichloromethane: ethyl acetate = 4:1); 1 H-NMR (DMSO-d 6 ): δ 1.80-2.00 (m, 4 H), 2.31 (s, 6 H), 2.61 ( t, 2 H), 4.07 (t, 2 H), 7.22 (d, 2 H), 7.30-7.40 (m, 2 H), 7.41 (s, 1 H), 7.66 (d, 2 H), 7.91 ( s, 1 H), 8.35 (s, 1 H), 8.67 (m, 3 H), 8.77 (s, 1 H), 9.51 (s, 1 H).

實施例52：1-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-苯基-5-(三氟甲基)-3-吡啶基]脲 Example 52: 1-(2-{4-[2-(2-Sideoxy-1-piperidyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)- 3-[2-phenyl-5-(trifluoromethyl)-3-pyridyl]urea

使用實施例24製造之化合物替代實施例8製造之化合物，進行與實施例9相同之操作，獲得具有以下物性值之本發明化合物。 Using the compound produced in Example 24 in place of the compound produced in Example 8, the same operation as in Example 9 was carried out to obtain a compound of the present invention having the following physical properties.

TLC：Rf 0.65(己烷：乙酸乙酯=1：4)；1H-NMR(DMSO-d6)：δ 1.75-1.98(m，4 H)，2.61(t，2 H)，4.07(t，2 H)，7.21(d，2 H)，7.50-7.64(m，3 H)，7.64-7.67(m，4 H)，7.90(s，1 H)，8.41(s，1 H)，8.66(s，2 H)，8.72(s，1 H)，8.75(s，1 H)，9.46(s，1 H)。 TLC: Rf 0.65 (hexane: ethyl acetate = 1 : 4); 1 H-NMR (DMSO-d 6 ): δ 1.75-1.98 (m, 4 H), 2.61 (t, 2 H), 4.07 (t , 2 H), 7.21 (d, 2 H), 7.50-7.64 (m, 3 H), 7.64-7.67 (m, 4 H), 7.90 (s, 1 H), 8.41 (s, 1 H), 8.66 (s, 2 H), 8.72 (s, 1 H), 8.75 (s, 1 H), 9.46 (s, 1 H).

實施例53：1-[2-(2-甲基苯基)-5-(三氟甲基)-3-吡啶基]-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 53: 1-[2-(2-Methylphenyl)-5-(trifluoromethyl)-3-pyridyl]-3-(2-{4-[2-(2-)oxy -1-piperidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

使用實施例44製造之化合物替代實施例8製造之化合物，進行與實施例9相同之操作，獲得具有以下物性值之本發明化合物。 Using the compound produced in Example 44 in place of the compound produced in Example 8, the same operation as in Example 9 was carried out to obtain a compound of the present invention having the following physical property.

TLC：Rf 0.65(己烷：乙酸乙酯=1：4)；1H-NMR(DMSO-d6)：δ 1.77-1.98(m，4 H)，2.07(s，3 H)，2.61(t，2 H)，4.07(t，2 H)，7.21(d，2 H)，7.27-7.50(m，4 H)，7.66(d，2 H)，7.91(s，1 H)，7.98(s，1 H)，8.65(s，2 H)，8.68(s，1 H)，8.88(s，1 H)，9.51(s，1 H)。 TLC: Rf 0.65 (hexane: ethyl acetate = 1 : 4); 1 H-NMR (DMSO-d 6 ): δ 1.77-1.98 (m, 4 H), 2.07 (s, 3 H), 2.61 (t , 2 H), 4.07 (t, 2 H), 7.21 (d, 2 H), 7.27-7.50 (m, 4 H), 7.66 (d, 2 H), 7.91 (s, 1 H), 7.98 (s , 1 H), 8.65 (s, 2 H), 8.68 (s, 1 H), 8.88 (s, 1 H), 9.51 (s, 1 H).

實施例54：1-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-苯基-5-(三氟甲基)-3-吡啶基]脲 Example 54: 1-(2-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)- 3-[2-phenyl-5-(trifluoromethyl)-3-pyridyl]urea

使用實施例49製造之化合物替代實施例5製造之化合物，使用實施例24製造之化合物替代實施例8製造之化合物，進行與實施例9相同之操作，獲得具有以下物性值之本發明化合物。 The compound produced in Example 49 was used in place of the compound produced in Example 5, and the compound produced in Example 24 was used in place of the compound produced in Example 8, and the same operation as in Example 9 was carried out to obtain a compound of the present invention having the following property values.

TLC：Rf 0.26(己烷：乙酸乙酯=1：4)；1H-NMR(DMSO-d6)：δ 2.16(q，2 H)，2.64(t，2 H)，4.04(t，2 H)，7.21(d，2 H)，7.54-7.67(m，7 H)，7.88(s，1 H)，8.41(s，1 H)，8.65(s，2 H)，8.71(s，1 H)，8.75(s，1 H)，9.45(s，1 H)。 TLC: Rf 0.26 (hexane: ethyl acetate = 1: 4); 1 H -NMR (DMSO-d 6): δ 2.16 (q, 2 H), 2.64 (t, 2 H), 4.04 (t, 2 H), 7.21 (d, 2 H), 7.54-7.67 (m, 7 H), 7.88 (s, 1 H), 8.41 (s, 1 H), 8.65 (s, 2 H), 8.71 (s, 1) H), 8.75 (s, 1 H), 9.45 (s, 1 H).

實施例55：1-[2-(2-甲基苯基)-5-(三氟甲基)-3-吡啶基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 55: 1-[2-(2-Methylphenyl)-5-(trifluoromethyl)-3-pyridyl]-3-(2-{4-[2-(2-)oxy -1-pyrrolidyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

使用實施例49製造之化合物替代實施例5製造之化合物，使用實施例44製造之化合物替代實施例8製造之化合物，進行與實 施例9相同之操作，獲得具有以下物性值之本發明化合物。 The compound produced in Example 49 was used in place of the compound produced in Example 5, and the compound produced in Example 44 was used instead of the compound produced in Example 8. The same procedure as in Example 9 gave the compound of the present invention having the following physical properties.

TLC：Rf 0.28(己烷：乙酸乙酯=1：4)；1H-NMR(DMSO-d6)：δ 2.06(s，3 H)，2.16(q，2 H)，2.64(t，2 H)，4.05(t，2 H)，7.20(d，2 H)，7.26-7.45(m，4 H)，7.66(d，2 H)，7.88(s，1 H)，7.97(s，1 H)，8.64(s，2 H)，8.67(s，1 H)，8.87(s，1 H)，9.51(s，1 H)。 TLC: Rf 0.28 (hexane: ethyl acetate = 1 : 4); 1 H-NMR (DMSO-d 6 ): δ 2.06 (s, 3 H), 2.16 (q, 2 H), 2.64 (t, 2) H), 4.05 (t, 2 H), 7.20 (d, 2 H), 7.26-7.45 (m, 4 H), 7.66 (d, 2 H), 7.88 (s, 1 H), 7.97 (s, 1) H), 8.64 (s, 2 H), 8.67 (s, 1 H), 8.87 (s, 1 H), 9.51 (s, 1 H).

實施例56：1-[2-(4-甲基苯基)-5-(三氟甲基)-3-吡啶基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 56: 1-[2-(4-Methylphenyl)-5-(trifluoromethyl)-3-pyridyl]-3-(2-{4-[2-(2-)oxy -1-pyrrolidyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

使用實施例49製造之化合物替代實施例5製造之化合物，使用實施例22製造之化合物替代實施例8製造之化合物，進行與實施例9相同之操作，獲得具有以下物性值之本發明化合物。 The compound produced in Example 49 was used in place of the compound produced in Example 5, and the compound produced in Example 22 was used in place of the compound produced in Example 8, and the same procedure as in Example 9 was carried out to obtain a compound of the present invention having the following property values.

TLC：Rf 0.27(己烷：乙酸乙酯=1：4)；1H-NMR(DMSO-d6)：δ 2.17(q，2 H)，2.04(s，3 H)，2.64(t，2 H)，4.05(t，2 H)，7.22(d，2 H)，7.37(d，2 H)，7.55(d，2 H)，7.67(d，2 H)，7.89(s，1 H)，8.38(s，1 H)，8.67(s，2 H)，8.70(s，1 H)，8.76(s，1 H)，9.48(s，1 H)。 TLC: Rf 0.27 (hexane: ethyl acetate = 1 : 4); 1 H-NMR (DMSO-d 6 ): δ 2.17 (q, 2 H), 2.04 (s, 3 H), 2.64 (t, 2) H), 4.05 (t, 2 H), 7.22 (d, 2 H), 7.37 (d, 2 H), 7.55 (d, 2 H), 7.67 (d, 2 H), 7.89 (s, 1 H) , 8.38 (s, 1 H), 8.67 (s, 2 H), 8.70 (s, 1 H), 8.76 (s, 1 H), 9.48 (s, 1 H).

實施例57：1-[2-(3-甲基苯基)-5-(三氟甲基)-3-吡啶基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 57: 1-[2-(3-Methylphenyl)-5-(trifluoromethyl)-3-pyridyl]-3-(2-{4-[2-(2-)oxy -1-pyrrolidyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

使用實施例49製造之化合物替代實施例5製造之化合物，使用實施例26製造之化合物替代實施例8製造之化合物，進行與實施例9相同之操作，獲得具有以下物性值之本發明化合物。 The compound produced in Example 49 was used in place of the compound produced in Example 5, and the compound produced in Example 26 was used in place of the compound produced in Example 8, and the same operation as in Example 9 was carried out to obtain a compound of the present invention having the following property values.

TLC：Rf 0.31(己烷：乙酸乙酯=1：4)； 1H-NMR(DMSO-d6)：δ 2.16(q，2 H)，2.40(s，3 H)，2.64(t，2 H)，4.05(t，2 H)，7.21(d，2 H)，7.30-7.45(m，4 H)，7.66(d，2 H)，7.89(s，1 H)，8.37(s，1 H)，8.66(s，2 H)，8.69(s，1 H)，8.76(s，1 H)，9.49(s，1 H)。 TLC: Rf 0.31 (hexane: ethyl acetate = 1 : 4); 1 H-NMR (DMSO-d 6 ): δ 2.16 (q, 2 H), 2.40 (s, 3 H), 2.64 (t, 2) H), 4.05 (t, 2 H), 7.21 (d, 2 H), 7.30-7.45 (m, 4 H), 7.66 (d, 2 H), 7.89 (s, 1 H), 8.37 (s, 1) H), 8.66 (s, 2 H), 8.69 (s, 1 H), 8.76 (s, 1 H), 9.49 (s, 1 H).

實施例58：1-(5-溴噻唑-2-基)氮呯-2-酮 Example 58: 1-(5-Bromothiazol-2-yl)azin-2-one

使用6-溴己醯氯替代5-溴戊醯氯，進行與實施例1→實施例2相同之操作，獲得具有以下物性值之標題化合物。 The same procedure as in Example 1 - Example 2 was carried out using 6-bromohexylfluorene chloride in place of 5-bromopentenyl chloride to obtain the title compound having the following property.

TLC：Rf 0.56(己烷：乙酸乙酯=3：1)。 TLC: Rf 0.56 (hexane: ethyl acetate = 3:1).

實施例59：1-[2-(3，4-二甲基苯基)-5-(三氟甲基)-3-吡啶基]-3-(2-{4-[2-(2-側氧基-1-氮呯基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 59: 1-[2-(3,4-Dimethylphenyl)-5-(trifluoromethyl)-3-pyridyl]-3-(2-{4-[2-(2- Oleoxy-1-indolyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

使用實施例58製造之化合物替代實施例18製造之化合物，進行與實施例21相同之操作，獲得具有以下物性值之本發明化合物。 Using the compound produced in Example 58 in place of the compound produced in Example 18, the same operation as in Example 21 was carried out to obtain a compound of the present invention having the following property values.

TLC：Rf 0.82(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 1.74(m，6 H)，2.32(s，6 H)，2.83(m，2 H)，4.46(m，2 H)，7.25(d，2 H)，7.35(m，3 H)，7.42(s，1 H)，7.65(d，2 H)，7.87(s，1 H)，8.35(s，1 H)8.67(s，2 H)，8.78(s，1 H)，9.51(s，1 H)。 TLC: Rf 0.82 (ethyl acetate); 1 H-NMR (DMSO -d 6): δ 1.74 (m, 6 H), 2.32 (s, 6 H), 2.83 (m, 2 H), 4.46 (m, 2 H), 7.25 (d, 2 H), 7.35 (m, 3 H), 7.42 (s, 1 H), 7.65 (d, 2 H), 7.87 (s, 1 H), 8.35 (s, 1 H) 8.67 (s, 2 H), 8.78 (s, 1 H), 9.51 (s, 1 H).

實施例60：2，2，2-三氯乙基(2-(1-甲基-1H-吡唑-4-基)-5-(三 氟甲基)吡啶-3-基)胺基甲酸酯 Example 60: 2,2,2-trichloroethyl (2-(1-methyl-1H-pyrazol-4-yl)-5-(three Fluoromethyl)pyridin-3-yl)carbamate

使用1-甲基-4-(4，4，5，5-四甲基-1，3，2-二硼烷-2-基)-1H-吡唑替代(6-(三氟甲基)吡啶-3-基)硼酸，使用2-氯-5-(三氟甲基)吡啶-3-胺替代2-氯-3-硝基-5-(三氟甲基)吡啶，進行與實施例6→實施例8相同之操作，獲得具有以下物性值之標題化合物。 Use 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-di Borane-2-yl)-1H-pyrazole in place of (6-(trifluoromethyl)pyridin-3-yl)boronic acid, using 2-chloro-5-(trifluoromethyl)pyridin-3-amine instead of 2 -Chloro-3-nitro-5-(trifluoromethyl)pyridine, the same procedure as in Example 6 - Example 8 was carried out to give the title compound.

TLC：Rf 0.70(乙酸乙酯)。 TLC: Rf 0.70 (EtOAc).

實施例61：1-[2-(1-甲基-1H-吡唑-4-基)-5-(三氟甲基)-3-吡啶基]-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 61:1-[2-(1-Methyl-1H-pyrazol-4-yl)-5-(trifluoromethyl)-3-pyridyl]-3-(2-{4-[2 -(2-Sideoxy-1-piperidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

使用實施例60製造之化合物替代實施例8製造之化合物，進行與實施例9相同之操作，獲得具有以下物性值之本發明化合物。 Using the compound produced in Example 60 in place of the compound produced in Example 8, the same operation as in Example 9 was carried out to obtain a compound of the present invention having the following physical properties.

TLC：Rf 0.63(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 1.75-1.98(m，4 H)，2.61(t，2 H)，3.93(s，3 H)，4.07(t，2 H)，7.23(d，2 H)，7.67(d，2 H)，7.91(s，1 H)，8.02(s，1 H)，8.35(s，1 H)，8.43(s，1 H)，8.58(s，1 H)，8.67(s，1 H)，8.73(s，2 H)，9.45(s，1 H)。 TLC: Rf 0.63 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 1.75-1.98 (m, 4 H), 2.61 (t, 2 H), 3.93 (s, 3 H), 4.07 ( t,2 H), 7.23 (d, 2 H), 7.67 (d, 2 H), 7.91 (s, 1 H), 8.02 (s, 1 H), 8.35 (s, 1 H), 8.43 (s, 1 H), 8.58 (s, 1 H), 8.67 (s, 1 H), 8.73 (s, 2 H), 9.45 (s, 1 H).

實施例62：3-(第三丁基)-1-(3，4-二甲基苯基)-1H-吡唑-5-胺 Example 62: 3-(Tert-butyl)-1-(3,4-dimethylphenyl)-1H-pyrazole-5-amine

於三甲基乙醯基乙腈(400mg)之甲苯(10mL)溶液中加入3，4-二甲基苯基肼鹽酸塩(520mg)及三乙胺(0.4mL)，加熱回流5小時。於反應混合物中加入飽和碳酸氫鈉水溶液，獲得之有機層以飽和食鹽水洗淨。獲得之有機層以無水硫酸鈉乾燥後減壓下進行濃縮。獲得之殘渣以矽膠管柱層析儀(己烷：乙酸乙酯=4：1)精製，獲得具有以下物性值之標題化合物(490mg)。 3,4-Dimethylphenylhydrazine hydrochloride (520 mg) and triethylamine (0.4 mL) were added to a solution of trimethylacetamidoacetonitrile (400 mg) in toluene (10 mL), and the mixture was refluxed for 5 hr. Saturated aqueous sodium hydrogencarbonate solution was added to the mixture, and the obtained organic layer was washed with brine. The obtained organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue obtained was purified by a silica gel column chromatography (hexane: ethyl acetate = 4:1) to give the title compound (490 mg).

TLC：Rf 0.41(己烷：乙酸乙酯=4：1)。 TLC: Rf 0.41 (hexane: ethyl acetate = 4:1).

實施例63：2，2，2-三氯乙基(3-(第三丁基)-1-(3，4-二甲基苯基)-1H-吡唑-5-基)胺基甲酸酯 Example 63: 2,2,2-Trichloroethyl (3-(t-butyl)-1-(3,4-dimethylphenyl)-1H-pyrazol-5-yl)amine A Acid ester

使用實施例62製造之化合物替代實施例7製造之化合物，進行與實施例8相同之操作，獲得具有以下物性值之標題化合物。 The compound produced in Example 62 was used in place of the compound produced in Example 7, and the same procedure as in Example 8 was carried out to obtain the title compound.

TLC：Rf 0.58(己烷：乙酸乙酯=4：1)。 TLC: Rf 0.58 (hexane: ethyl acetate = 4:1).

實施例64：1-(3-(第三丁基)-1-(3，4-二甲基苯基)-1H-吡唑-5-基)-3-(2-(4-(4，4，5，5-四甲基-1，3，2-二硼烷-2-基)苯氧基)嘧啶-5-基)脲 Example 64: 1-(3-(Tertiarybutyl)-1-(3,4-dimethylphenyl)-1H-pyrazol-5-yl)-3-(2-(4-(4) ,4,5,5-tetramethyl-1,3,2-di Borane-2-yl)phenoxy)pyrimidin-5-yl)urea

使用實施例63製造之化合物替代實施例8製造之化合物，實施例13製造之化合物替代實施例5製造之化合物，進行與實施例9→實施例20相同之操作，獲得具有以下物性值之標題化合物。 The compound produced in Example 63 was used in place of the compound produced in Example 8, and the compound produced in Example 13 was used in place of the compound produced in Example 5, and the same operation as in Example 9 → Example 20 was carried out to obtain the title compound having the following physical property. .

TLC：Rf 0.56(二氯甲烷：乙酸乙酯=4：1)。 TLC: Rf 0.56 (dichloromethane: ethyl acetate = 4:1).

實施例65 Example 65

使用實施例64製造之化合物替代實施例20製造之化合物，使用相當之5-溴噻唑衍生物替代實施例18製造之化合物，進行與實施例21相同之操作，獲得具有以下物性值之本發明化合物。 Using the compound produced in Example 64 in place of the compound produced in Example 20, and using the equivalent 5-bromothiazole derivative in place of the compound produced in Example 18, the same operation as in Example 21 was carried out to obtain a compound of the present invention having the following physical properties. .

實施例65-1：1-[1-(3，4-二甲基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 65-1:1-[1-(3,4-Dimethylphenyl)-3-(2-methyl-2-propyl)-1H-pyrazole-5-yl]-3-( 2-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.31(己烷：乙酸乙酯=3：7)；1H-NMR(DMSO-d6)：δ 1.25(s，9 H)，2.10-2.23(m，2 H)，2.27(s，6 H)，2.64(t，2 H)，4.05(t，2 H)，6.33(s，1 H)，7.15-7.28(m，5 H)，7.66(d，2 H)，7.89(s，1 H)，8.54(s，1 H)，8.64(s，2 H)，9.18(s，1 H)。 TLC: Rf 0.31 (hexane: ethyl acetate = 3:7); 1 H-NMR (DMSO-d 6 ): δ 1.25 (s, 9 H), 2.10-2.23 (m, 2 H), 2.27 (s) , 6 H), 2.64 (t, 2 H), 4.05 (t, 2 H), 6.33 (s, 1 H), 7.15-7.28 (m, 5 H), 7.66 (d, 2 H), 7.89 (s , 1 H), 8.54 (s, 1 H), 8.64 (s, 2 H), 9.18 (s, 1 H).

實施例65-2：1-[1-(3，4-二甲基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 65-2: 1-[1-(3,4-Dimethylphenyl)-3-(2-methyl-2-propyl)-1H-pyrazole-5-yl]-3-( 2-{4-[2-(2-Sideoxy-1-piperidyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.31(己烷：乙酸乙酯=1：2)；1H-NMR(DMSO-d6)：δ 1.26(s，9 H)，1.76-2.00(m，4 H)，2.27(s，6 H)，2.61(t，2 H)，4.07(t，2 H)，6.33(s，1 H)，7.16-7.29(m，5 H)，7.65(d，2 H)，7.91(s，1 H)，8.54(s，1 H)，8.65(s，2 H)，9.19(s，1 H)。 TLC: Rf 0.31 (hexane: ethyl acetate = 1:2); 1 H-NMR (DMSO-d 6 ): δ 1.26 (s, 9 H), 1.76 - 2.00 (m, 4 H), 2.27 (s) , 6 H), 2.61 (t, 2 H), 4.07 (t, 2 H), 6.33 (s, 1 H), 7.16-7.29 (m, 5 H), 7.65 (d, 2 H), 7.91 (s , 1 H), 8.54 (s, 1 H), 8.65 (s, 2 H), 9.19 (s, 1 H).

實施例66 Example 66

使用相當之肼衍生物替代(3，4-二甲基苯基)肼鹽酸塩，使用4-溴苯酚、或使用相當之4-溴苯酚衍生物或6-溴吡啶-3-醇替代4-溴苯酚，使用相當之5-溴噻唑衍生物替代實施例18製造之化合物，進行實施例62→實施例63→實施例12→實施例13→實施例19→實施例20→實施例21相同之操作，獲得具有以下物性值之本發明化合物。 Substituting a comparable hydrazine derivative for (3,4-dimethylphenyl)hydrazine hydrochloride, using 4-bromophenol, or using an equivalent 4-bromophenol derivative or 6-bromopyridin-3-ol instead of 4- The bromophenol was replaced with the equivalent 5-bromothiazole derivative in the same manner as the compound produced in Example 18, and the same procedure as in Example 62→Example 63→Example 12→Example 13→Example 19→Example 20→Example 21 was carried out. Operation, a compound of the present invention having the following physical property values is obtained.

實施例66-1：1-[1-(2，3-二氫-1H-茚-5-基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 66-1:1-[1-(2,3-Dihydro-1H-indol-5-yl)-3-(2-methyl-2-propyl)-1H-pyrazole-5-yl ]-3-(2-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.58(二氯甲烷：乙酸乙酯：甲醇=8：4：1)； 1H-NMR(DMSO-d6)：δ 1.26(s.9 H)，2.00-2.22(m，4 H)，2.64(t，2 H)，2.84-2.97(m，4 H)，4.05(t，2 H)，6.33(s，1 H)，7.16-7.26(m，3 H)，7.27-7.36(m，2 H)，7.66(d，2 H)，7.89(s，1 H)，8.56(s，1 H)，8.65(s，2 H)，9.19(s，1 H)。 TLC: Rf 0.58 (dichloromethane: ethyl acetate:methanol = 8:4:1); 1 H-NMR (DMSO-d 6 ): δ 1.26 (s.9 H), 2.00-2.22 (m, 4 H) ), 2.64(t, 2 H), 2.84-2.97 (m, 4 H), 4.05 (t, 2 H), 6.33 (s, 1 H), 7.16-7.26 (m, 3 H), 7.27-7.36 ( m, 2 H), 7.66 (d, 2 H), 7.89 (s, 1 H), 8.56 (s, 1 H), 8.65 (s, 2 H), 9.19 (s, 1 H).

實施例66-2：1-[1-(2，3-二氫-1H-茚-5-基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{2-氟-4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 66-2: 1-[1-(2,3-Dihydro-1H-indol-5-yl)-3-(2-methyl-2-propyl)-1H-pyrazole-5-yl ]-3-(2-{2-Fluoro-4-[2-(2-o-oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl Urea

TLC：Rf 0.34(己烷：乙酸乙酯=1：2)；1H-NMR(DMSO-d6)：δ 1.26(s，9 H)，2.06(t，2 H)，2.14(t，2 H)，2.65(t，2 H)，2.89(t，2 H)，2.91(t，2 H)，4.05(t，2 H)，6.33(s，1 H)，7.21(dd，1 H)，7.32-7.46(m，4 H)，7.73(dd，1 H)，7.99(s，1 H)，8.56(s，1 H)，8.66(s，2 H)，9.20(s，1 H)。 TLC: Rf 0.34 (hexane: ethyl acetate = 1: 2); 1 H -NMR (DMSO-d 6): δ 1.26 (s, 9 H), 2.06 (t, 2 H), 2.14 (t, 2 H), 2.65 (t, 2 H), 2.89 (t, 2 H), 2.91 (t, 2 H), 4.05 (t, 2 H), 6.33 (s, 1 H), 7.21. (dd, 1 H) , 7.32-7.46 (m, 4 H), 7.73 (dd, 1 H), 7.99 (s, 1 H), 8.56 (s, 1 H), 8.66 (s, 2 H), 9.20 (s, 1 H) .

實施例66-3：1-[1-(2，3-二氫-1H-茚-5-基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 66-3: 1-[1-(2,3-Dihydro-1H-indol-5-yl)-3-(2-methyl-2-propyl)-1H-pyrazole-5-yl ]-3-(2-{4-[2-(2-Sideoxy-1-piperidyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.38(己烷：乙酸乙酯=1：2)；1H-NMR(DMSO-d6)：δ 1.26(s，9 H)，1.82(m，2 H)，1.93(m，2 H)，2.06(m，2 H)，2.61(t，2 H)，2.91(m，4 H)，4.06(t，2 H)，6.33(s，1 H)，7.21(d，3 H)，7.32(m，2 H)，7.65(d，2 H)，7.90(s，1 H)，8.56(s，1 H)，8.64(s，2 H)，9.18(s，1 H)。 TLC: Rf 0.38 (hexane: ethyl acetate = 1:2); 1 H-NMR (DMSO-d 6 ): δ 1.26 (s, 9 H), 1.82 (m, 2 H), 1.93 (m, 2) H), 2.06 (m, 2 H), 2.61 (t, 2 H), 2.91 (m, 4 H), 4.06 (t, 2 H), 6.33 (s, 1 H), 7.21. (d, 3 H) , 7.32 (m, 2 H), 7.65 (d, 2 H), 7.90 (s, 1 H), 8.56 (s, 1 H), 8.64 (s, 2 H), 9.18 (s, 1 H).

實施例66-4：1-[1-(2，3-二氫-1H-茚-5-基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{3-氟-4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 66-4: 1-[1-(2,3-Dihydro-1H-indol-5-yl)-3-(2-methyl-2-propyl)-1H-pyrazole-5-yl ]-3-(2-{3-Fluoro-4-[2-(2-o-oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl Urea

TLC：Rf 0.33(甲醇：乙酸乙酯=1：9)；1H-NMR(DMSO-d6)：δ 1.26(s，9 H)，2.06(m，2 H)，2.17(m，2 H)，2.65(t，2 H)，2.90(tt，4 H)，4.06(t，2 H)，6.34(s，1 H)，7.11(dd，1 H)，7.22(dd，1 H)，7.32(m，3 H)，7.81(t，1 H)，7.95(s，1 H)，8.58(s，1 H)，8.68(s，2 H)，9.23(s，1 H)。 TLC: Rf 0.33 (methanol: ethyl acetate = 1:9); 1 H-NMR (DMSO-d 6 ): δ 1.26 (s, 9 H), 2.06 (m, 2 H), 2.17 (m, 2 H) ), 2.65 (t, 2 H), 2.90 (tt, 4 H), 4.06 (t, 2 H), 6.34 (s, 1 H), 7.11 (dd, 1 H), 7.22 (dd, 1 H), 7.32 (m, 3 H), 7.81 (t, 1 H), 7.95 (s, 1 H), 8.58 (s, 1 H), 8.68 (s, 2 H), 9.23 (s, 1 H).

實施例66-5：1-(2-{2-氯-4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[1-(2，3-二氫-1H-茚-5-基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]脲 Example 66-5: 1-(2-{2-Chloro-4-[2-(2-o-oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}- 5-pyrimidinyl-3-[1-(2,3-dihydro-1H-indol-5-yl)-3-(2-methyl-2-propyl)-1H-pyrazole-5-yl Urea

TLC：Rf 0.70(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 1.26(s，9 H)，2.06(m，2 H)，2.17(m，2 H)，2.65(t，2 H)，2.90(m，4 H)，4.06(t，2 H)，6.33(s，1 H)，7.21(d，1 H)，7.32-7.41(m，3 H)7.63(d，1 H)，7.90(s，1 H)，8.01(s，1 H)，8.57(s，1 H)，8.65(s，2 H)，9.19(s，1 H)。 TLC: Rf 0.70 (ethyl acetate); 1 H-NMR (DMSO -d 6): δ 1.26 (s, 9 H), 2.06 (m, 2 H), 2.17 (m, 2 H), 2.65 (t, 2 H), 2.90 (m, 4 H), 4.06 (t, 2 H), 6.33 (s, 1 H), 7.21 (d, 1 H), 7.32-7.41 (m, 3 H) 7.63 (d, 1 H), 7.90 (s, 1 H), 8.01 (s, 1 H), 8.57 (s, 1 H), 8.65 (s, 2 H), 9.19 (s, 1 H).

實施例66-6：1-[1-(2，3-二氫-1H-茚-5-基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-氮呯基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 66-6: 1-[1-(2,3-Dihydro-1H-indol-5-yl)-3-(2-methyl-2-propyl)-1H-pyrazole-5-yl ]-3-(2-{4-[2-(2-Sideoxy-1-indolyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.80(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 1.26(s，9 H)，1.73(m，6 H)，2.06(m，2 H)，2.81-2.94(m，6 H)，4.45(t，2 H)，6.33(s，1 H)，7.21(d，3 H)，7.32-7.47(m，2 H)，7.64(d，2 H)，7.86(s，1 H)，8.56(s，1 H)，8.65(s，2 H)，9.18(s，1 H)。 TLC: Rf 0.80 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 1.26 (s, 9 H), 1.73 (m, 6 H), 2.06 (m, 2 H), 2.81-2.94 ( m,6 H), 4.45 (t, 2 H), 6.33 (s, 1 H), 7.21 (d, 3 H), 7.32-7.47 (m, 2 H), 7.64 (d, 2 H), 7.86 ( s, 1 H), 8.56 (s, 1 H), 8.65 (s, 2 H), 9.18 (s, 1 H).

實施例66-7：1-{1-[3-(羥基甲基)-4-甲基苯基]-3-(2-甲基-2-丙基)-1H-吡唑-5-基}-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 66-7: 1-{1-[3-(Hydroxymethyl)-4-methylphenyl]-3-(2-methyl-2-propyl)-1H-pyrazole-5-yl }-3-(2-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.57(乙酸乙酯：甲醇=9：1)；1H-NMR(DMSO-d6)：δ 1.26(s，9 H)，2.16(m，2 H)，2.26(s，3 H)，2.64(t，2 H)，4.05(t，2 H)，4.53(d，2 H)，5.24(t，1 H)，6.33(s，1 H)，7.20-7.25(m，4 H)，7.48(s，1 H)，7.67(d，2 H)，7.89(s，1 H)，8.55(s，1 H)，8.65(s，2 H)，9.17(s，1 H)。 TLC: Rf 0.57 (ethyl acetate: methanol = 9: 1); 1 H -NMR (DMSO-d 6): δ 1.26 (s, 9 H), 2.16 (m, 2 H), 2.26 (s, 3 H ), 2.64 (t, 2 H), 4.05 (t, 2 H), 4.53 (d, 2 H), 5.24 (t, 1 H), 6.33 (s, 1 H), 7.20-7.25 (m, 4 H) ), 7.48 (s, 1 H), 7.67 (d, 2 H), 7.89 (s, 1 H), 8.55 (s, 1 H), 8.65 (s, 2 H), 9.17 (s, 1 H).

實施例66-8：1-{1-[4-(羥基甲基)-3-甲基苯基]-3-(2-甲基-2-丙基)-1H-吡唑-5-基}-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 66-8: 1-{1-[4-(Hydroxymethyl)-3-methylphenyl]-3-(2-methyl-2-propyl)-1H-pyrazole-5-yl }-3-(2-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.60(乙酸乙酯：甲醇=9：1)；1H-NMR(DMSO-d6)：δ 1.26(s，9 H)，2.16(m，2 H)，2.28(s.3 H)，2.64(t，2 H)，4.05(t，2 H)，4.53(d，2 H)，5.20(t，1 H)，6.34(s，1 H)，7.20-7.29(m，4 H)，7.48(d，1 H)，7.67(d，2 H)，7.89(s，1 H)，8.57(s，1 H)，8.65(s，2 H)，9.21(s，1 H)。 TLC: Rf 0.60 (ethyl acetate:methanol = 9:1); 1 H-NMR (DMSO-d 6 ): δ 1.26 (s, 9 H), 2.16 (m, 2 H), 2.28 (s. ), 2.64 (t, 2 H), 4.05 (t, 2 H), 4.53 (d, 2 H), 5.20 (t, 1 H), 6.34 (s, 1 H), 7.20-7.29 (m, 4 H) ), 7.48 (d, 1 H), 7.67 (d, 2 H), 7.89 (s, 1 H), 8.57 (s, 1 H), 8.65 (s, 2 H), 9.21. (s, 1 H).

實施例66-9：1-{3-(2-甲基-2-丙基)-1-[4-甲基-3-(三氟甲基)苯基]-1H-吡唑-5-基}-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 66-9: 1-{3-(2-Methyl-2-propyl)-1-[4-methyl-3-(trifluoromethyl)phenyl]-1H-pyrazole-5- -3-}-3-(2-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.59(二氯甲烷：乙酸乙酯：甲醇=8：4：1)； 1H-NMR(DMSO-d6)：δ 1.27(s，9 H)，2.10-2.24(m，2 H)，2.49(s，3 H)，2.64(t，2 H)，4.05(t，2 H)，6.37(s，1 H)，7.21(d，2 H)，7.54-7.80(m，5 H)，7.89(s，1 H)，8.63(s，2 H)，8.69(s，1 H)，9.20(s，1 H)。 TLC: Rf 0.59 (dichloromethane: ethyl acetate:methanol = 8:4:1); 1 H-NMR (DMSO-d 6 ): δ 1.27 (s, 9 H), 2.10-2.24 (m, 2 H) ), 2.49 (s, 3 H), 2.64 (t, 2 H), 4.05 (t, 2 H), 6.37 (s, 1 H), 7.21 (d, 2 H), 7.54-7.80 (m, 5 H ), 7.89 (s, 1 H), 8.63 (s, 2 H), 8.69 (s, 1 H), 9.20 (s, 1 H).

實施例66-10：1-[3-(2-甲基-2-丙基)-1-(3，4，5-三甲基苯基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 66-10: 1-[3-(2-Methyl-2-propyl)-1-(3,4,5-trimethylphenyl)-1H-pyrazol-5-yl]-3 -(2-{4-[2-(2-Sideoxy-1-piperidyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.73(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 1.25(s，9 H)，1.83-2.00(m，4 H)，2.17(s，3 H)，2.30(s，6 H)，2.61(t，2 H)，4.07(t，2 H)，6.33(s，1 H)，7.10(s，2 H)，7.20(d，2 H)，7.65(d，2 H)，7.91(s，1 H)8.51(s，1 H)，8.65(s，2 H)，9.19(s，1 H)。 TLC: Rf 0.73 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 1.25 (s, 9 H), 1.83-2.00 (m, 4 H), 2.17 (s, 3 H), 2.30 ( s,6 H), 2.61 (t, 2 H), 4.07 (t, 2 H), 6.33 (s, 1 H), 7.10 (s, 2 H), 7.20 (d, 2 H), 7.65 (d, 2 H), 7.91 (s, 1 H) 8.51 (s, 1 H), 8.65 (s, 2 H), 9.19 (s, 1 H).

實施例66-11：1-[3-(2-甲基-2-丙基)-1-(3，4，5-三甲基苯基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 66-11: 1-[3-(2-Methyl-2-propyl)-1-(3,4,5-trimethylphenyl)-1H-pyrazol-5-yl]-3 -(2-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.80(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 1.26(s，9 H)，2.16(m，5 H)，2.29(s，6 H)，2.63(t，2 H)，4.05(t，2 H)，6.32(s，1 H)，7.10(s，2 H)，7.20(d，2 H)，7.65(d，2 H)，7.88(s，1 H)8.51(s，1 H)，8.64(s，2 H)，9.18(s，1 H)。 TLC: Rf 0.80 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 1.26 (s, 9 H), 2.16 (m, 5 H), 2.29 (s, 6 H), 2.63 (t, 2 H), 4.05 (t, 2 H), 6.32 (s, 1 H), 7.10 (s, 2 H), 7.20 (d, 2 H), 7.65 (d, 2 H), 7.88 (s, 1 H) ) 8.51 (s, 1 H), 8.64 (s, 2 H), 9.18 (s, 1 H).

實施例66-12：1-[1-(4-氟苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 66-12: 1-[1-(4-Fluorophenyl)-3-(2-methyl-2-propyl)-1H-pyrazole-5-yl]-3-(2-{4 -[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.51(二氯甲烷：乙酸乙酯：甲醇=8：4：1)； 1H-NMR(DMSO-d6)：δ 1.27(s，9 H)，2.10-2.23(m，2 H)，2.64(t，2 H)，4.05(t，2 H)，6.35(s，1 H)，7.21(d，2 H)，7.35(t，2 H)，7.54(dd，2 H)，7.66(d，2 H)，7.89(s，1 H)，8.62(s，1 H)，8.65(s，2 H)，9.17(s，1 H)。 TLC: Rf 0.51 (dichloromethane: ethyl acetate:methanol = 8:4:1); 1 H-NMR (DMSO-d 6 ): δ 1.27 (s, 9 H), 2.10-2.23 (m, 2 H) ), 2.64 (t, 2 H), 4.05 (t, 2 H), 6.35 (s, 1 H), 7.21 (d, 2 H), 7.35 (t, 2 H), 7.54 (dd, 2 H), 7.66 (d, 2 H), 7.89 (s, 1 H), 8.62 (s, 1 H), 8.65 (s, 2 H), 9.17 (s, 1 H).

實施例66-13：1-[1-(4-甲氧基-3，5-二甲基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 66-13: 1-[1-(4-Methoxy-3,5-dimethylphenyl)-3-(2-methyl-2-propyl)-1H-pyrazole-5- 3-(2-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.51(二氯甲烷：乙酸乙酯：甲醇=8：4：1)；1H-NMR(DMSO-d6)：δ 1.25(s，9 H)，2.10-2.23(m，2 H)，2.27(s，6 H)，2.64(t，2 H)，3.69(s，3 H)，4.05(t，2 H)，5.75(s，1 H)，6.33(s，1 H)，7.14(s，1 H)，7.21(d，2 H)，7.66(d，2 H)，7.89(s，1 H)，8.57(s，1 H)，8.65(s，2 H)，9.18(s，1 H)。 TLC: Rf 0.51 (dichloromethane: ethyl acetate:methanol = 8:4:1); 1 H-NMR (DMSO-d 6 ): δ 1.25 (s, 9 H), 2.10-2.23 (m, 2 H) ), 2.27 (s, 6 H), 2.64 (t, 2 H), 3.69 (s, 3 H), 4.05 (t, 2 H), 5.75 (s, 1 H), 6.33 (s, 1 H), 7.14 (s, 1 H), 7.21 (d, 2 H), 7.66 (d, 2 H), 7.89 (s, 1 H), 8.57 (s, 1 H), 8.65 (s, 2 H), 9.18 ( s, 1 H).

實施例66-14：1-{3-(2-甲基-2-丙基)-1-[4-(三氟甲基)苯基]-1H-吡唑-5-基}-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 66-14: 1-{3-(2-Methyl-2-propyl)-1-[4-(trifluoromethyl)phenyl]-1H-pyrazole-5-yl}-3- (2-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.58(二氯甲烷：乙酸乙酯：甲醇=8：4：1)；1H-NMR(DMSO-d6)：δ 1.28(s，9 H)，2.10-2.23(m，2 H)，2.64(t，2 H)，4.05(t，2 H)，6.41(s，1 H)，7.21(d，2 H)，7.66(d，2 H)，7.78(d，2 H)，7.70-7.82(m，3 H)，8.66(s，2 H)，8.80(s，1 H)，9.23(s，1 H)。 TLC: Rf 0.58 (dichloromethane: ethyl acetate:methanol = 8:4:1); 1 H-NMR (DMSO-d 6 ): δ 1.28 (s, 9 H), 2.10-2.23 (m, 2 H) ), 2.64 (t, 2 H), 4.05 (t, 2 H), 6.41 (s, 1 H), 7.21 (d, 2 H), 7.66 (d, 2 H), 7.78 (d, 2 H), 7.70-7.82 (m, 3 H), 8.66 (s, 2 H), 8.80 (s, 1 H), 9.23 (s, 1 H).

實施例66-15：1-[3-(2-甲基-2-丙基)-1-苯基-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 66-15: 1-[3-(2-Methyl-2-propyl)-1-phenyl-1H-pyrazol-5-yl]-3-(2-{4-[2-( 2-sided oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.51(二氯甲烷：乙酸乙酯：甲醇=8：4：1)； 1H-NMR(DMSO-d6)：δ 1.26(s，9 H)，2.10-2.23(m，2 H)，2.63(t，2 H)，4.04(t，2 H)，6.35(s，1 H)，7.20(d，2 H)，7.35-7.43(m，1 H)，7.47-7.53(m，4 H)，7.66(d，2 H)，7.88(s，1 H)，8.64(s，3 H)，9.19(s，1 H)。 TLC: Rf 0.51 (dichloromethane: ethyl acetate:methanol = 8:4:1); 1 H-NMR (DMSO-d 6 ): δ 1.26 (s, 9 H), 2.10-2.23 (m, 2 H) ), 2.63 (t, 2 H), 4.04 (t, 2 H), 6.35 (s, 1 H), 7.20 (d, 2 H), 7.35-7.43 (m, 1 H), 7.47-7.53 (m, 4 H), 7.66 (d, 2 H), 7.88 (s, 1 H), 8.64 (s, 3 H), 9.19 (s, 1 H).

實施例66-16：1-[1-(4-甲基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 66-16: 1-[1-(4-Methylphenyl)-3-(2-methyl-2-propyl)-1H-pyrazol-5-yl]-3-(2-{ 4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.49(二氯甲烷：乙酸乙酯：甲醇=8：4：1)；1H-NMR(DMSO-d6)：δ 1.26(s，9 H)，2.10-2.23(m，2 H)，2.35(s，3 H)，2.63(t，2 H)，4.04(t，2 H)，6.32(s，1 H)，7.19(d，2 H)，7.29(d，2 H)，7.36(d，2 H)，7.65(d，2 H)，7.88(s，1 H)，8.56(s，1 H)，8.63(s，2 H)，9.18(s，1 H)。 TLC: Rf 0.49 (dichloromethane: ethyl acetate:methanol = 8:4:1); 1 H-NMR (DMSO-d 6 ): δ 1.26 (s, 9 H), 2.10-2.23 (m, 2 H) ), 2.35 (s, 3 H), 2.63 (t, 2 H), 4.04 (t, 2 H), 6.32 (s, 1 H), 7.19 (d, 2 H), 7.29 (d, 2 H), 7.36 (d, 2 H), 7.65 (d, 2 H), 7.88 (s, 1 H), 8.56 (s, 1 H), 8.63 (s, 2 H), 9.18 (s, 1 H).

實施例66-17：1-[1-均三甲苯基-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 66-17: 1-[1-Hexyltolyl-3-(2-methyl-2-propyl)-1H-pyrazol-5-yl]-3-(2-{4-[2 -(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.51(二氯甲烷：乙酸乙酯：甲醇=8：4：1)；1H-NMR(DMSO-d6)：δ 1.25(s，9 H)，1.87(s，6 H)，2.10-2.23(m，2 H)，2.32(s，3 H)，2.64(t，2 H)，4.05(t，2 H)，6.33(s，1 H)，7.04(s，2 H)，7.20(d，2 H)，7.66(d，2 H)，7.88(s，1 H)，8.28(s，1 H)，8.63(s，2 H)，9.03(s，1 H)。 TLC: Rf 0.51 (dichloromethane: ethyl acetate: methanol = 8: 4: 1); 1 H-NMR (DMSO-d 6): δ 1.25 (s, 9 H), 1.87 (s, 6 H), 2.10-2.23 (m, 2 H), 2.32 (s, 3 H), 2.64 (t, 2 H), 4.05 (t, 2 H), 6.33 (s, 1 H), 7.04 (s, 2 H), 7.20 (d, 2 H), 7.66 (d, 2 H), 7.88 (s, 1 H), 8.28 (s, 1 H), 8.63 (s, 2 H), 9.03 (s, 1 H).

實施例66-18：1-[1-(2-甲基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 66-18: 1-[1-(2-Methylphenyl)-3-(2-methyl-2-propyl)-1H-pyrazol-5-yl]-3-(2-{ 4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.51(二氯甲烷：乙酸乙酯：甲醇=8：4：1)； 1H-NMR(DMSO-d6)：δ 1.26(s，9 H)，1.99(s，3 H)，2.10-2.23(m，2 H)，2.64(t，2 H)，4.05(t，2 H)，6.33(s，1 H)，7.20(d，2 H)，7.28-7.44(m，4 H)，7.65(d，2 H)，7.88(s，1 H)，8.38(s，1 H)，8.62(s，2 H)，9.06(s，1 H)。 TLC: Rf 0.51 (dichloromethane: ethyl acetate:methanol = 8:4:1); 1 H-NMR (DMSO-d 6 ): δ 1.26 (s, 9 H), 1.99 (s, 3 H), 2.10-2.23 (m, 2 H), 2.64 (t, 2 H), 4.05 (t, 2 H), 6.33 (s, 1 H), 7.20 (d, 2 H), 7.28-7.44 (m, 4 H) ), 7.65 (d, 2 H), 7.88 (s, 1 H), 8.38 (s, 1 H), 8.62 (s, 2 H), 9.06 (s, 1 H).

實施例66-19：1-[1-(2，3-二氫-1-苯并呋喃-5-基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 66-19: 1-[1-(2,3-Dihydro-1-benzofuran-5-yl)-3-(2-methyl-2-propyl)-1H-pyrazole-5 -yl]-3-(2-{4-[2-(2-o-oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.50(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 1.25(s，9 H)，2.16(q，2 H)，2.64(t，2 H)，3.23(t，2 H)，4.05(t，2 H)，4.59(t，2 H)，6.31(s，1 H)，6.86(d，1 H)，7.31-7.14(m，4 H)，7.67(d，2 H)，7.89(s，1 H)，8.50(s，1 H)，8.65(s，2 H)，9.17(s，1 H)。 TLC: Rf 0.50 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 1.25 (s, 9 H), 2.16 (q, 2 H), 2.64 (t, 2 H), 3.23 (t, 2 H), 4.05 (t, 2 H), 4.59 (t, 2 H), 6.31 (s, 1 H), 6.86 (d, 1 H), 7.31-7.14 (m, 4 H), 7.67 (d, 2 H), 7.89 (s, 1 H), 8.50 (s, 1 H), 8.65 (s, 2 H), 9.17 (s, 1 H).

實施例66-20：1-[1-(2，3-二甲基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 66-20: 1-[1-(2,3-Dimethylphenyl)-3-(2-methyl-2-propyl)-1H-pyrazol-5-yl]-3-( 2-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.47(二氯甲烷：乙酸乙酯：甲醇=8：4：1)；1H-NMR(DMSO-d6)：δ 1.25(s，9 H)，1.82(s，3 H)，2.10-2.23(m，2 H)，2.32(s，3 H)，2.64(t，2 H)，4.05(t，2 H)，6.34(s，1 H)，7.12-7.28(m，4 H)，7.30-7.36(m，1 H)，7.66(d，2 H)，7.88(s，1 H)，8.32(s，1 H)，8.62(s，2 H)，9.06(s，1 H)。 TLC: Rf 0.47 (dichloromethane: ethyl acetate: methanol = 8: 4: 1); 1 H-NMR (DMSO-d 6): δ 1.25 (s, 9 H), 1.82 (s, 3 H), 2.10-2.23 (m, 2 H), 2.32 (s, 3 H), 2.64 (t, 2 H), 4.05 (t, 2 H), 6.34 (s, 1 H), 7.12-7.28 (m, 4 H) ), 7.30-7.36 (m, 1 H), 7.66 (d, 2 H), 7.88 (s, 1 H), 8.32 (s, 1 H), 8.62 (s, 2 H), 9.06 (s, 1 H) ).

實施例66-21：1-[1-(4-甲氧基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 66-21:1-[1-(4-Methoxyphenyl)-3-(2-methyl-2-propyl)-1H-pyrazole-5-yl]-3-(2- {4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.44(二氯甲烷：乙酸乙酯：甲醇=8：4：1)；1H-NMR(DMSO-d6)：δ 1.26(s，9 H)，2.10-2.23(m，2 H)，2.64(t，2 H)，3.80(s，3 H)，4.05(t，2 H)，6.31(s，1 H)，7.05(d，2 H)，7.20(d，2 H)，7.39(d，2 H)，7.66(d，2 H)，7.88(s，1 H)，8.52(s，1 H)，8.64(s，2 H)，9.17(s，1 H)。 TLC: Rf 0.44 (dichloromethane: ethyl acetate:methanol = 8:4:1); 1 H-NMR (DMSO-d 6 ): δ 1.26 (s, 9 H), 2.10-2.23 (m, 2 H) ), 2.64 (t, 2 H), 3.80 (s, 3 H), 4.05 (t, 2 H), 6.31 (s, 1 H), 7.05 (d, 2 H), 7.20 (d, 2 H), 7.39 (d, 2 H), 7.66 (d, 2 H), 7.88 (s, 1 H), 8.52 (s, 1 H), 8.64 (s, 2 H), 9.17 (s, 1 H).

實施例66-22：1-[1-(4-氟-2-甲基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 66-22: 1-[1-(4-Fluoro-2-methylphenyl)-3-(2-methyl-2-propyl)-1H-pyrazol-5-yl]-3- (2-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.55(二氯甲烷：乙酸乙酯：甲醇=8：4：1)；1H-NMR(DMSO-d6)：δ 1.25(s，9 H)，1.97(s，3 H)，2.10-2.24(m，2 H)，2.64(t，2 H)，4.04(t，2 H)，6.32(s，1 H)，7.14-7.24(m，3 H)，7.26-7.33(m，1 H)，7.35-7.42(m，1 H)，7.66(d，2 H)，7.88(s，1 H)，8.40(s，1 H)，8.62(s，2 H)，9.00(s，1 H)。 TLC: Rf 0.55 (dichloromethane: ethyl acetate: methanol = 8: 4: 1); 1 H-NMR (DMSO-d 6): δ 1.25 (s, 9 H), 1.97 (s, 3 H), 2.10-2.24 (m, 2 H), 2.64 (t, 2 H), 4.04 (t, 2 H), 6.32 (s, 1 H), 7.14-7.24 (m, 3 H), 7.26-7.33 (m, 1 H), 7.35-7.42 (m, 1 H), 7.66 (d, 2 H), 7.88 (s, 1 H), 8.40 (s, 1 H), 8.62 (s, 2 H), 9.00 (s, 1 H).

實施例66-23：1-[1-(2-氟苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 66-23: 1-[1-(2-Fluorophenyl)-3-(2-methyl-2-propyl)-1H-pyrazole-5-yl]-3-(2-{4 -[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.62(二氯甲烷：乙酸乙酯：甲醇=8：4：1)；1H-NMR(DMSO-d6)：δ 1.26(s，9 H)，2.10-2.24(m，2 H)，2.64(t，2 H)，4.05(t，2 H)，6.36(s，1 H)，7.20(d，2 H)，7.32-7.60(m，4 H)，7.66(d，2 H)，7.89(s，1 H)，8.61(s，1 H)，8.63(s，2 H)，9.04(s，1 H)。 TLC: Rf 0.62 (dichloromethane: ethyl acetate:methanol = 8:4:1); 1 H-NMR (DMSO-d 6 ): δ 1.26 (s, 9 H), 2.10-2.24 (m, 2 H) ), 2.64 (t, 2 H), 4.05 (t, 2 H), 6.36 (s, 1 H), 7.20 (d, 2 H), 7.32-7.60 (m, 4 H), 7.66 (d, 2 H) ), 7.89 (s, 1 H), 8.61 (s, 1 H), 8.63 (s, 2 H), 9.04 (s, 1 H).

實施例66-24：1-[1-(2-氟-3-甲基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 66-24: 1-[1-(2-Fluoro-3-methylphenyl)-3-(2-methyl-2-propyl)-1H-pyrazole-5-yl]-3- (2-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.63(二氯甲烷：乙酸乙酯：甲醇=8：4：1)；1H-NMR(DMSO-d6)：δ 1.25(s，9 H)，2.10-2.24(m，2 H)，2.32-2.36(m，3 H)，2.66(t，2 H)，4.05(t，2 H)，6.36(s，1 H)，7.18-7.28(m，3 H)，7.30-7.37(m，1 H)，7.40-7.48(m，1 H)，7.66(d，2 H)，7.89(s，1 H)，8.59(s，1 H)，8.65(s，2 H)，9.04(s，1 H)。 TLC: Rf 0.63 (dichloromethane: ethyl acetate:methanol = 8:4:1); 1 H-NMR (DMSO-d 6 ): δ 1.25 (s, 9 H), 2.10-2.24 (m, 2 H) ), 2.32 - 2.36 (m, 3 H), 2.66 (t, 2 H), 4.05 (t, 2 H), 6.36 (s, 1 H), 7.18-7.28 (m, 3 H), 7.30-7.37 ( m,1 H), 7.40-7.48 (m, 1 H), 7.66 (d, 2 H), 7.89 (s, 1 H), 8.59 (s, 1 H), 8.65 (s, 2 H), 9.04 ( s, 1 H).

實施例66-25：1-[1-(3-氟苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 66-25: 1-[1-(3-Fluorophenyl)-3-(2-methyl-2-propyl)-1H-pyrazole-5-yl]-3-(2-{4 -[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.64(二氯甲烷：乙酸乙酯：甲醇=8：4：1)；1H-NMR(DMSO-d6)：δ 1.25(s，9 H)，2.10-2.24(m，2 H)，2.64(t，2 H)，4.05(t，2 H)，6.38(s，1 H)，7.21(d，2 H)，7.36-7.44(m，2 H)，7.48-7.70(m，4 H)，7.89(s，1 H)，8.62(s，2 H)，8.72(s，1 H)，9.24(s，1 H)。 TLC: Rf 0.64 (dichloromethane: ethyl acetate:methanol = 8:4:1); 1 H-NMR (DMSO-d 6 ): δ 1.25 (s, 9 H), 2.10-2.24 (m, 2 H) ), 2.64 (t, 2 H), 4.05 (t, 2 H), 6.38 (s, 1 H), 7.21 (d, 2 H), 7.36-7.44 (m, 2 H), 7.48-7.70 (m, 4 H), 7.89 (s, 1 H), 8.62 (s, 2 H), 8.72 (s, 1 H), 9.24 (s, 1 H).

實施例66-26：1-[1-(2-甲基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Examples 66-26: 1-[1-(2-Methylphenyl)-3-(2-methyl-2-propyl)-1H-pyrazol-5-yl]-3-(2-{ 4-[2-(2-Sideoxy-1-piperidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.33(乙酸乙酯：己烷=2：1)；1H-NMR(DMSO-d6)：δ 1.25(s，9 H)，1.83(m，2 H)，1.93(m，2 H)，1.99(s，3 H)，2.61(t，2 H)，4.06(t，2 H)，6.34(s，1 H)，7.21(d，2 H)，7.30-7.44(m，4 H)，7.66(d，2 H)，7.91(s，1 H)，8.39(s，1 H)，8.63(s，2 H)，9.06(s，1 H)。 TLC: Rf 0.33 (ethyl acetate: hexane = 2: 1); 1 H -NMR (DMSO-d 6): δ 1.25 (s, 9 H), 1.83 (m, 2 H), 1.93 (m, 2 H), 1.99 (s, 3 H), 2.61 (t, 2 H), 4.06 (t, 2 H), 6.34 (s, 1 H), 7.21 (d, 2 H), 7.30-7.44 (m, 4) H), 7.66 (d, 2 H), 7.91 (s, 1 H), 8.39 (s, 1 H), 8.63 (s, 2 H), 9.06 (s, 1 H).

實施例66-27：甲基3-[3-(2-甲基-2-丙基)-5-{[(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)胺基甲醯基]胺基}-1H-吡唑-1-基]苯甲酸酯 Example 66-27: methyl 3-[3-(2-methyl-2-propyl)-5-{[(2-{4-[2-(2-o-oxy-1-pyrrolidinyl) )-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)aminomethylindenyl]amino}-1H-pyrazol-1-yl]benzoate

TLC：Rf 0.46(二氯甲烷：乙酸乙酯：甲醇=8：4：1)；1H-NMR(DMSO-d6)：δ 1.28(s，9 H)，2.10-2.24(m，2 H)，2.64(t，2 H)，3.86(s，3 H)，4.05(t，2 H)，6.38(s，1 H)，7.18-7.25(m，2 H)，7.62-7.70(m，3 H)，7.82(d，1 H)，7.89(s，1 H)，7.94(d，1 H)，8.07(s，1 H)，8.64(s，2 H)，8.73(s，1 H)，9.20(s，1 H)。 TLC: Rf 0.46 (dichloromethane: ethyl acetate:methanol = 8:4:1); 1 H-NMR (DMSO-d 6 ): δ 1.28 (s, 9 H), 2.10-2.24 (m, 2 H) ), 2.64 (t, 2 H), 3.86 (s, 3 H), 4.05 (t, 2 H), 6.38 (s, 1 H), 7.18-7.25 (m, 2 H), 7.62-7.70 (m, 3 H), 7.82 (d, 1 H), 7.89 (s, 1 H), 7.94 (d, 1 H), 8.07 (s, 1 H), 8.64 (s, 2 H), 8.73 (s, 1 H) ), 9.20 (s, 1 H).

實施例66-28：N-{4-[3-(2-甲基-2-丙基)-5-{[(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)胺基甲醯基]胺基}-1H-吡唑-1-基]苯基}乙醯胺 Example 66-28: N-{4-[3-(2-methyl-2-propyl)-5-{[(2-{4-[2-(2-Sideoxy-1-pyrrolidine) -1,3-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)aminomethylindenyl]amino}-1H-pyrazol-1-yl]phenyl}acetamide

TLC：Rf 0.24(二氯甲烷：乙酸乙酯：甲醇=8：4：1)；1H-NMR(DMSO-d6)：δ 1.26(s，9 H)，2.05(s，3 H)，2.10-2.24(m，2 H)，2.64(t，2 H)，4.05(t，2 H)，6.29(s，1 H)，7.20(d，2 H)，7.41(d，2 H)，7.60-7.75(m，4 H)，7.88(s，1 H)，8.65(s，2 H)， 9.07(br s，1 H)，9.71(br s，1 H)，10.09(s，1 H)。 TLC: Rf 0.24 (dichloromethane: ethyl acetate: methanol = 8: 4: 1); 1 H-NMR (DMSO-d 6): δ 1.26 (s, 9 H), 2.05 (s, 3 H), 2.10-2.24 (m, 2 H), 2.64 (t, 2 H), 4.05 (t, 2 H), 6.29 (s, 1 H), 7.20 (d, 2 H), 7.41 (d, 2 H), 7.60-7.75 (m, 4 H), 7.88 (s, 1 H), 8.65 (s, 2 H), 9.07 (br s, 1 H), 9.71 (br s, 1 H), 10.09 (s, 1 H) ).

實施例66-29：1-[1-(1，3-苯并二茂-5-基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Examples 66-29: 1-[1-(1,3-Benzene) -5-5-yl)-3-(2-methyl-2-propyl)-1H-pyrazol-5-yl]-3-(2-{4-[2-(2- oxo-1) -pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.39(二氯甲烷：乙酸乙酯：甲醇=8：4：1)；1H-NMR(DMSO-d6)：δ 1.25(s，9 H)，2.10-2.24(m，2 H)，2.64(t，2 H)，4.05(t，2 H)，6.10(s，2 H)，6.31(s，1 H)，6.52(s，1 H)，6.93(dd，1 H)，7.05(t，1 H)，7.21(d，2 H)，7.66(d，2 H)，7.89(s，1 H)，8.55(s，1 H)，8.65(s，2 H)，9.18(s，1 H)。 TLC: Rf 0.39 (dichloromethane: ethyl acetate:methanol = 8:4:1); 1 H-NMR (DMSO-d 6 ): δ 1.25 (s, 9 H), 2.10-2.24 (m, 2 H) ), 2.64 (t, 2 H), 4.05 (t, 2 H), 6.10 (s, 2 H), 6.31 (s, 1 H), 6.52 (s, 1 H), 6.93 (dd, 1 H), 7.05 (t, 1 H), 7.21 (d, 2 H), 7.66 (d, 2 H), 7.89 (s, 1 H), 8.55 (s, 1 H), 8.65 (s, 2 H), 9.18 ( s, 1 H).

實施例66-30：1-[3-(2-甲基-2-丙基)-1-苯基-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 66-30: 1-[3-(2-Methyl-2-propyl)-1-phenyl-1H-pyrazol-5-yl]-3-(2-{4-[2-( 2-sided oxy-1-piperidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.65(己烷：乙酸乙酯=1：4)；1H-NMR(DMSO-d6)：δ 1.27(s，9 H)，1.75-1.99(m，4 H)，2.61(t，2 H)，4.07(s，2 H)，6.36(s，1 H)，7.21(d，2 H)，7.35-7.40(m，1 H)，7.40-7.55(m，4 H)，7.65(d，2 H)，7.91(s，1 H)，8.65(s，1 H)，8.65(s，2 H)，9.20(s，1 H)。 TLC: Rf 0.65 (hexane: ethyl acetate = 1 : 4); 1 H-NMR (DMSO-d 6 ): δ 1.27 (s, 9 H), 1.75-1.99 (m, 4 H), 2.61 (t) , 2 H), 4.07 (s, 2 H), 6.36 (s, 1 H), 7.21 (d, 2 H), 7.35-7.40 (m, 1 H), 7.40-7.55 (m, 4 H), 7.65 (d, 2 H), 7.91 (s, 1 H), 8.65 (s, 1 H), 8.65 (s, 2 H), 9.20 (s, 1 H).

實施例66-31：1-[1-(2，3-二甲氧基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 66-31:1-[1-(2,3-Dimethoxyphenyl)-3-(2-methyl-2-propyl)-1H-pyrazole-5-yl]-3- (2-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.51(二氯甲烷：乙酸乙酯：甲醇=8：4：1)；1H-NMR(DMSO-d6)：δ 1.25(s，9 H)，2.10-2.24(m，2 H)，2.64(t，2 H)，3.52(s，3 H)，3.87(s，3 H)，4.05(t，2 H)，6.33(s，1 H)，6.93-7.00(m，1 H)，7.17-7.26(m，4 H)，7.66(d，2 H)，7.89(s，1 H)，8.32(s，1 H)，8.64(s，2 H)，9.19(s，1 H)。 TLC: Rf 0.51 (dichloromethane: ethyl acetate:methanol = 8:4:1); 1 H-NMR (DMSO-d 6 ): δ 1.25 (s, 9 H), 2.10-2.24 (m, 2 H) ), 2.64 (t, 2 H), 3.52 (s, 3 H), 3.87 (s, 3 H), 4.05 (t, 2 H), 6.33 (s, 1 H), 6.93-7.00 (m, 1 H) ), 7.17-7.26 (m, 4 H), 7.66 (d, 2 H), 7.89 (s, 1 H), 8.32 (s, 1 H), 8.64 (s, 2 H), 9.19 (s, 1 H) ).

實施例66-32：1-[1-(2-氟-4-甲氧基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 66-32: 1-[1-(2-Fluoro-4-methoxyphenyl)-3-(2-methyl-2-propyl)-1H-pyrazol-5-yl]-3 -(2-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.51(二氯甲烷：乙酸乙酯：甲醇=8：4：1)；1H-NMR(DMSO-d6)：δ 1.25(s，9 H)，2.10-2.24(m，2 H)，2.64(t，2 H)，3.84(s，3 H)，4.05(t，2 H)，6.33(s，1 H)，6.90-6.96(m，1 H)，7.05-7.15(m，1 H)，7.21(d，2 H)，7.43(t，1 H)，7.66(d，2 H)，7.89(s，1 H)，8.55(s，1 H)，8.65(s，2 H)，9.03(s，1 H)。 TLC: Rf 0.51 (dichloromethane: ethyl acetate:methanol = 8:4:1); 1 H-NMR (DMSO-d 6 ): δ 1.25 (s, 9 H), 2.10-2.24 (m, 2 H) ), 2.64 (t, 2 H), 3.84 (s, 3 H), 4.05 (t, 2 H), 6.33 (s, 1 H), 6.90-6.96 (m, 1 H), 7.05-7.15 (m, 1 H), 7.21 (d, 2 H), 7.43 (t, 1 H), 7.66 (d, 2 H), 7.89 (s, 1 H), 8.55 (s, 1 H), 8.65 (s, 2 H) ), 9.03 (s, 1 H).

實施例66-33：1-{1-[2-氟-4-(三氟甲基)苯基]-3-(2-甲基-2-丙基)-1H-吡唑-5-基}-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 66-33: 1-{1-[2-Fluoro-4-(trifluoromethyl)phenyl]-3-(2-methyl-2-propyl)-1H-pyrazole-5-yl }-3-(2-{4-[2-(2-Sideoxy-1-piperidyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.59(己烷：乙酸乙酯=1：3)；1H-NMR(CDCl3)：δ 1.30-1.38(m，9 H)，1.83-2.07(m，4 H)，2.55(t，2 H)，4.18(t，2 H)，6.42(s，1 H)，7.15(d，2 H)，7.19-7.28(m，1 H)，7.38-7.61(m，5 H)，7.64(s，1 H)，7.68(s，1 H)，8.60(s，2 H)。 TLC: Rf 0.59 (hexane: ethyl acetate = 1 : 3); 1 H-NMR (CDCl 3 ): δ 1.30-1.38 (m, 9 H), 1.83-2.07 (m, 4 H), 2.55 (t) , 2 H), 4.18 (t, 2 H), 6.42 (s, 1 H), 7.15 (d, 2 H), 7.19-7.28 (m, 1 H), 7.38-7.61 (m, 5 H), 7.64 (s, 1 H), 7.68 (s, 1 H), 8.60 (s, 2 H).

實施例66-34：1-[1-(2-氯-4-甲基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 66-34: 1-[1-(2-Chloro-4-methylphenyl)-3-(2-methyl-2-propyl)-1H-pyrazol-5-yl]-3- (2-{4-[2-(2-Sideoxy-1-piperidyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.35(己烷：乙酸乙酯=1：3)；1H-NMR(CDCl3)：δ 1.35(s，9 H)，1.88-2.07(m，4 H)，2.35(s，3 H)，2.68(t，2 H)，4.17(t，2 H)，6.34(s，1 H)，6.43(s，1 H)，7.03(br s，1 H)，7.12-7.21(m，3 H)，7.26-7.33(m，2 H)，7.58(d，2 H)，7.63(s，1 H)，8.55(s，2 H)。 TLC: Rf 0.35 (hexane: ethyl acetate = 1 : 3); 1 H-NMR (CDCl 3 ): δ 1.35 (s, 9 H), 1.88-2.07 (m, 4 H), 2.35 (s, 3) H), 2.68 (t, 2 H), 4.17 (t, 2 H), 6.34 (s, 1 H), 6.43 (s, 1 H), 7.03 (br s, 1 H), 7.12-7.21 (m, 3 H), 7.26-7.33 (m, 2 H), 7.58 (d, 2 H), 7.63 (s, 1 H), 8.55 (s, 2 H).

實施例66-35：1-[1-(2，5-二甲基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 66-35: 1-[1-(2,5-Dimethylphenyl)-3-(2-methyl-2-propyl)-1H-pyrazole-5-yl]-3-( 2-{4-[2-(2-Sideoxy-1-piperidyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.68(二氯甲烷：乙酸乙酯：甲醇=8：4：1)；1H-NMR(DMSO-d6)：δ 1.25(s，9 H)，1.77-1.88(m，2 H)，1.93(s，3 H)，2.33(s，3 H)，2.35-2.45(m，2 H)，2.61(t，2 H)，4.07(t，2 H)，6.33(s，1 H)，7.12-7.32(m，5 H)，7.65(d，2 H)，7.91(s，1 H)，8.37(s，1 H)，8.63(s，2 H)，9.08(s，1 H)。 TLC: Rf 0.68 (dichloromethane: ethyl acetate:methanol = 8:4:1); 1 H-NMR (DMSO-d 6 ): δ 1.25 (s, 9 H), 1.77-1.88 (m, 2 H) ), 1.93 (s, 3 H), 2.33 (s, 3 H), 2.35-2.45 (m, 2 H), 2.61 (t, 2 H), 4.07 (t, 2 H), 6.33 (s, 1 H) ), 7.12-7.32 (m, 5 H), 7.65 (d, 2 H), 7.91 (s, 1 H), 8.37 (s, 1 H), 8.63 (s, 2 H), 9.08 (s, 1 H) ).

實施例66-36：1-[1-(2-氟苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 66-36: 1-[1-(2-Fluorophenyl)-3-(2-methyl-2-propyl)-1H-pyrazole-5-yl]-3-(2-{4 -[2-(2-Sideoxy-1-piperidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.58(二氯甲烷：乙酸乙酯：甲醇=8：4：1)；1H-NMR(DMSO-d6)：δ 1.26(s，9 H)，1.77-2.00(m，4 H)，2.61(t，2 H)，4.07(t，2 H)，6.36(s，1 H)，7.21(d，2 H)，7.33-7.60(m，4 H)，7.65(d，2 H)，7.91(s，1 H)，8.61(s，1 H)，8.64(s，2 H)，9.04(s，1 H)。 TLC: Rf 0.58 (dichloromethane: ethyl acetate:methanol = 8:4:1); 1 H-NMR (DMSO-d 6 ): δ 1.26 (s, 9 H), 1.77-2.00 (m, 4 H) ), 2.61 (t, 2 H), 4.07 (t, 2 H), 6.36 (s, 1 H), 7.21 (d, 2 H), 7.33-7.60 (m, 4 H), 7.65 (d, 2 H) ), 7.91 (s, 1 H), 8.61 (s, 1 H), 8.64 (s, 2 H), 9.04 (s, 1 H).

實施例66-37：1-[1-(2-氟-4-甲基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 66-37: 1-[1-(2-Fluoro-4-methylphenyl)-3-(2-methyl-2-propyl)-1H-pyrazol-5-yl]-3- (2-{4-[2-(2-Sideoxy-1-piperidyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.61(二氯甲烷：乙酸乙酯：甲醇=8：4：1)；1H-NMR(DMSO-d6)：δ 1.25(s，9 H)，1.77-2.00(m，4 H)，2.40(s，3 H)，2.61(t，2 H)，4.07(t，2 H)，6.34(s，1 H)，7.16-7.25(m，3 H)，7.30(d，1 H)，7.39(t，1 H)，7.65(d，2 H)，7.91(s，1 H)，8.56(s，1 H)，8.64(s，2 H)，9.05(s，1 H)。 TLC: Rf 0.61 (dichloromethane: ethyl acetate:methanol = 8:4:1); 1 H-NMR (DMSO-d 6 ): δ 1.25 (s, 9 H), 1.77-2.00 (m, 4 H) ), 2.40 (s, 3 H), 2.61 (t, 2 H), 4.07 (t, 2 H), 6.34 (s, 1 H), 7.16-7.25 (m, 3 H), 7.30 (d, 1 H) ), 7.39 (t, 1 H), 7.65 (d, 2 H), 7.91 (s, 1 H), 8.56 (s, 1 H), 8.64 (s, 2 H), 9.05 (s, 1 H).

實施例66-38：1-[1-(4-氟苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 66-38: 1-[1-(4-Fluorophenyl)-3-(2-methyl-2-propyl)-1H-pyrazole-5-yl]-3-(2-{4 -[2-(2-Sideoxy-1-piperidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.68(二氯甲烷：乙酸乙酯：甲醇=8：4：1)；1H-NMR(DMSO-d6)：δ 1.27(s，9 H)，1.77-2.00(m，4 H)，2.61(t，2 H)，4.07(t，2 H)，6.35(s，1 H)，7.21(d，2 H)，7.35(t，2 H)，7.50-7.59(m，2 H)，7.66(d，2 H)，7.91(s，1 H)，8.62(s，1 H)，8.65(s，2 H)，9.17(s，1 H)。 TLC: Rf 0.68 (dichloromethane: ethyl acetate:methanol = 8:4:1); 1 H-NMR (DMSO-d 6 ): δ 1.27 (s, 9 H), 1.77-2.00 (m, 4 H) ), 2.61 (t, 2 H), 4.07 (t, 2 H), 6.35 (s, 1 H), 7.21 (d, 2 H), 7.35 (t, 2 H), 7.50-7.59 (m, 2 H) ), 7.66 (d, 2 H), 7.91 (s, 1 H), 8.62 (s, 1 H), 8.65 (s, 2 H), 9.17 (s, 1 H).

實施例66-39：1-[1-(3-丁氧基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 66-39: 1-[1-(3-Butoxyphenyl)-3-(2-methyl-2-propyl)-1H-pyrazol-5-yl]-3-(2- {4-[2-(2-Sideoxy-1-piperidyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.59(己烷：乙酸乙酯=1：3)；1H-NMR(CDCl3)：δ 0.88-0.98(m，3 H)，1.35(s，9 H)，1.43(dd，2 H)，1.64-1.77(m，2 H)，1.83-2.05(m，4 H)，2.53(t，2 H)，3.91(t，1 H)，4.16(t，2 H)，6.43(s，1 H)，6.82-6.87(m，1 H)，6.98-7.04(m，2 H)，7.10(s，1 H)，7.17(d，2 H)，7.22-7.30(m，2 H)，7.47(s，1 H)，7.53(d，2 H)，7.65(s，1 H)，8.61(s，2 H)。 TLC: Rf 0.59 (hexane: ethyl acetate = 1 : 3); 1 H-NMR (CDCl 3 ): δ 0.88-0.98 (m, 3 H), 1.35 (s, 9 H), 1.43 (dd, 2) H), 1.64-1.77 (m, 2 H), 1.83-2.05 (m, 4 H), 2.53 (t, 2 H), 3.91 (t, 1 H), 4.16 (t, 2 H), 6.43 (s) , 1 H), 6.82-6.87 (m, 1 H), 6.98-7.04 (m, 2 H), 7.10 (s, 1 H), 7.17 (d, 2 H), 7.22-7.30 (m, 2 H) , 7.47 (s, 1 H), 7.53 (d, 2 H), 7.65 (s, 1 H), 8.61 (s, 2 H).

實施例66-40：1-[3-(2-甲基-2-丙基)-1-(4-丙基苯基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5- 嘧啶基)脲 Example 66-40: 1-[3-(2-Methyl-2-propyl)-1-(4-propylphenyl)-1H-pyrazol-5-yl]-3-(2-{ 4-[2-(2-Sideoxy-1-piperidinyl)-1,3-thiazol-5-yl]phenoxy}-5- Pyrimidinyl urea

TLC：Rf 0.67(己烷：乙酸乙酯=1：3)；1H-NMR(DMSO-d6)：δ 0.94(t，3 H)，1.36(s，9 H)，1.57-1.69(m，2 H)，1.86-2.07(m，4 H)，2.54-2.69(m，4 H)，4.17(t，2 H)，6.37(s，1 H)，6.53(s，1 H)，6.88(br s，1 H)，7.19(d，2 H)，7.24(br s，2 H)，7.35-7.41(m，2 H)，7.59(d，2 H)，7.65(s，1 H)，8.56(s，2 H)。 TLC: Rf 0.67 (hexane: ethyl acetate = 1:3); 1 H-NMR (DMSO-d 6 ): δ 0.94 (t, 3 H), 1.36 (s, 9 H), 1.57-1.69 (m) , 2 H), 1.86-2.07 (m, 4 H), 2.54-2.69 (m, 4 H), 4.17 (t, 2 H), 6.37 (s, 1 H), 6.53 (s, 1 H), 6.88 (br s, 1 H), 7.19 (d, 2 H), 7.24 (br s, 2 H), 7.35-7.41 (m, 2 H), 7.59 (d, 2 H), 7.65 (s, 1 H) , 8.56 (s, 2 H).

實施例66-41：1-[1-(3-氯-4-甲基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 66-41:1-[1-(3-Chloro-4-methylphenyl)-3-(2-methyl-2-propyl)-1H-pyrazole-5-yl]-3- (2-{4-[2-(2-Sideoxy-1-piperidyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.33(己烷：乙酸乙酯=1：1)；1H-NMR(DMSO-d6)：δ 1.26(s，9 H)，1.77-1.98(m，4 H)，2.36(s，3 H)，2.60(t，2 H)，4.06(t，2 H)，6.35(s，1 H)，7.20(d，2 H)，7.38-7.43(m，1 H)，7.45-7.50(m，1 H)，7.55-7.58(m，1 H)，7.64(d，2 H)，7.90(s，1 H)，8.64(s，2 H)，8.66(s，1 H)，9.20(s，1 H)。 TLC: Rf 0.33 (hexane: ethyl acetate = 1:1); 1 H-NMR (DMSO-d 6 ): δ 1.26 (s, 9 H), 1.77-1.98 (m, 4 H), 2.36 (s) , 3 H), 2.60 (t, 2 H), 4.06 (t, 2 H), 6.35 (s, 1 H), 7.20 (d, 2 H), 7.38-7.43 (m, 1 H), 7.45-7.50 (m, 1 H), 7.55-7.58 (m, 1 H), 7.64 (d, 2 H), 7.90 (s, 1 H), 8.64 (s, 2 H), 8.66 (s, 1 H), 9.20 (s, 1 H).

實施例66-42：1-{3-(2-甲基-2-丙基)-1-[4-(三氟甲基)苯基]-1H-吡唑-5-基}-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Examples 66-42: 1-{3-(2-Methyl-2-propyl)-1-[4-(trifluoromethyl)phenyl]-1H-pyrazole-5-yl}-3- (2-{4-[2-(2-Sideoxy-1-piperidyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.12(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 1.29(s，9 H)，1.83(m，2 H)，1.92(m，2 H)，2.61(t，2 H)，4.67(t，2 H)，6.41(s，1 H)，7.19(d，2 H)，7.65(d，2 H)，7.77(d，2 H)，7.87(d，2 H)，7.90(s，1 H)，8.65(s，2 H)，8.79(s，1 H)，9.21(s，1 H)。 TLC: Rf 0.12 (ethyl acetate); 1 H-NMR (DMSO -d 6): δ 1.29 (s, 9 H), 1.83 (m, 2 H), 1.92 (m, 2 H), 2.61 (t, 2 H), 4.67 (t, 2 H), 6.41 (s, 1 H), 7.19 (d, 2 H), 7.65 (d, 2 H), 7.77 (d, 2 H), 7.87 (d, 2 H) ), 7.90 (s, 1 H), 8.65 (s, 2 H), 8.79 (s, 1 H), 9.21 (s, 1 H).

實施例66-43：1-[1-(4-甲基苯基)-3-(2-甲基-2-丙基)-1H-吡 唑-5-基]-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Examples 66-43: 1-[1-(4-Methylphenyl)-3-(2-methyl-2-propyl)-1H-pyridyl Zyrid-5-yl]-3-(2-{4-[2-(2-o-oxy-1-piperidyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidine Urea

TLC：Rf 0.23(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 1.26(s，9 H)，1.83(m，2 H)，1.92(m，2 H)，2.42(s，3 H)，2.61(t，2 H)，4.07(t，2 H)，6.33(s，1 H)，7.20(dd，2 H)，7.30(d，2 H)，7.37(d，2 H)，7.65(dd，2 H)，7.90(s，1 H)，8.56(s，1 H)，8.64(s，2 H)，9.18(s，1 H)。 TLC: Rf 0.23 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 1.26 (s, 9 H), 1.83 (m, 2 H), 1.92 (m, 2 H), 2.42 (s, 3 H), 2.61 (t, 2 H), 4.07 (t, 2 H), 6.33 (s, 1 H), 7.20 (dd, 2 H), 7.30 (d, 2 H), 7.37 (d, 2 H) ), 7.65 (dd, 2 H), 7.90 (s, 1 H), 8.56 (s, 1 H), 8.64 (s, 2 H), 9.18 (s, 1 H).

實施例66-44：1-[1-(3-甲氧基-4-甲基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 66-44: 1-[1-(3-Methoxy-4-methylphenyl)-3-(2-methyl-2-propyl)-1H-pyrazole-5-yl]- 3-(2-{4-[2-(2-Sideoxy-1-piperidyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.71(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 1.27(s，9 H)，1.85(m，2 H)，1.93(m，2 H)，2.19(s，3 H)，2.61(t，2 H)，3.80(s，3 H)，4.07(t，2 H)，6.35(s，1 H)，6.97(d，1 H)，7.03(s，1 H)7.20(d，2 H)，7.26(d，1 H)，7.65(d，2 H)，7.91(s，1 H)，8.55(s，1 H)，8.65(s，2 H)，9.24(s，1 H)。 TLC: Rf 0.71 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 1.27 (s, 9 H), 1.85 (m, 2 H), 1.93 (m, 2 H), 2.19 (s, 3 H), 2.61 (t, 2 H), 3.80 (s, 3 H), 4.07 (t, 2 H), 6.35 (s, 1 H), 6.97 (d, 1 H), 7.03 (s, 1 H) ) 7.20 (d, 2 H), 7.26 (d, 1 H), 7.65 (d, 2 H), 7.91 (s, 1 H), 8.55 (s, 1 H), 8.65 (s, 2 H), 9.24 (s, 1 H).

實施例66-45：1-[1-(3-甲基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 66-45: 1-[1-(3-Methylphenyl)-3-(2-methyl-2-propyl)-1H-pyrazol-5-yl]-3-(2-{ 4-[2-(2-Sideoxy-1-piperidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.63(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 1.27(s，9 H)，1.83(m，2 H)，1.93(m，2 H)，2.37(s，3 H)，2.61(t，2 H)，4.07(t，2 H)，6.35(s，1 H)，7.20(d，3 H)，7.28(m，2 H)7.39(t，1 H)，7.67(d，2 H)，7.91(s，1 H)，8.61(s，1 H)，8.65(s，2 H)，9.20(s，1 H)。 TLC: Rf 0.63 (ethyl acetate); 1 H-NMR (DMSO -d 6): δ 1.27 (s, 9 H), 1.83 (m, 2 H), 1.93 (m, 2 H), 2.37 (s, 3 H), 2.61 (t, 2 H), 4.07 (t, 2 H), 6.35 (s, 1 H), 7.20 (d, 3 H), 7.28 (m, 2 H) 7.39 (t, 1 H) , 7.67 (d, 2 H), 7.91 (s, 1 H), 8.61 (s, 1 H), 8.65 (s, 2 H), 9.20 (s, 1 H).

實施例66-46：1-[1-(3，4-二氫-2H-色烯-6-基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 66-46: 1-[1-(3,4-Dihydro-2H-chromen-6-yl)-3-(2-methyl-2-propyl)-1H-pyrazole-5- 3-(2-{4-[2-(2-Sideoxy-1-piperidyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.39(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 1.13(s，9 H)，1.71-1.85(m，6 H)，2.49(t，2 H)，2.65(t，2 H)，3.95(t，2 H)，4.05(t，2 H)，6.19(s，1 H)，6.73(d，1 H)，7.04(m，2 H)，7.09(d，2 H)7.54(d，2 H)，7.79(s，1 H)，8.39(s，1 H)，8.53(s，2 H)，9.06(s，1 H)。 TLC: Rf 0.39 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 1.13 (s, 9 H), 1.71-1.85 (m, 6 H), 2.49 (t, 2 H), 2.65 ( t,2 H), 3.95 (t, 2 H), 4.05 (t, 2 H), 6.19 (s, 1 H), 6.73 (d, 1 H), 7.04 (m, 2 H), 7.09 (d, 2 H) 7.54 (d, 2 H), 7.79 (s, 1 H), 8.39 (s, 1 H), 8.53 (s, 2 H), 9.06 (s, 1 H).

實施例66-47：1-{1-[4-(3-羥基丙基)苯基]-3-(2-甲基-2-丙基)-1H-吡唑-5-基}-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 66-47: 1-{1-[4-(3-Hydroxypropyl)phenyl]-3-(2-methyl-2-propyl)-1H-pyrazole-5-yl}-3 -(2-{4-[2-(2-Sideoxy-1-piperidyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.50(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 1.27(s，9 H)，1.70-1.93(m，6 H)，2.59-2.72(m，4 H)，3.39(q，2 H)，4.07(t，2 H)，4.47(t，1 H)，6.35(s，1 H)，7.22(m，3 H)，7.32(m，2 H)，7.41(t，1 H)，7.65(d，2 H)，7.91(s，1 H)，8.61(s，1 H)，8.64(s，2 H)，9.21(s，1 H)。 TLC: Rf 0.50 (ethyl acetate); 1 H-NMR (DMSO -d 6): δ 1.27 (s, 9 H), 1.70-1.93 (m, 6 H), 2.59-2.72 (m, 4 H), 3.39 (q, 2 H), 4.07 (t, 2 H), 4.47 (t, 1 H), 6.35 (s, 1 H), 7.22 (m, 3 H), 7.32 (m, 2 H), 7.41 ( t, 1 H), 7.65 (d, 2 H), 7.91 (s, 1 H), 8.61 (s, 1 H), 8.64 (s, 2 H), 9.21. (s, 1 H).

實施例66-48：1-[1-(3-甲氧基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 66-48: 1-[1-(3-Methoxyphenyl)-3-(2-methyl-2-propyl)-1H-pyrazol-5-yl]-3-(2- {4-[2-(2-Sideoxy-1-piperidyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.51(乙酸乙酯)； 1H-NMR(DMSO-d6)：δ 1.27(s，9 H)，1.83-1.94(m，4 H)，2.61(t，2 H)，3.79(s，3 H)，4.07(t，2 H)，6.36(s，1 H)，6.97(dd，1 H)，7.08(d，2 H)，7.20(d，2 H)，7.41(t，1 H)，7.65(d，2 H)，7.91(s，1 H)，8.63(s，1 H)，8.65(s，2 H)，9.24(s，1 H)。 TLC: Rf 0.51 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 1.27 (s, 9 H), 1.83-1.94 (m, 4 H), 2.61 (t, 2 H), 3.79 ( s, 3 H), 4.07 (t, 2 H), 6.36 (s, 1 H), 6.97 (dd, 1 H), 7.08 (d, 2 H), 7.20 (d, 2 H), 7.41 (t, 1 H), 7.65 (d, 2 H), 7.91 (s, 1 H), 8.63 (s, 1 H), 8.65 (s, 2 H), 9.24 (s, 1 H).

實施例66-49：1-[1-(2，3-二氫-1，4-苯并二英-6-基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Examples 66-49: 1-[1-(2,3-Dihydro-1,4-benzoic) -6-yl)-3-(2-methyl-2-propyl)-1H-pyrazol-5-yl]-3-(2-{4-[2-(2-trioxy-1) -piperidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.49(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 1.25(s，9 H)，1.80-2.00(m，4 H)，2.61(t，2 H)，4.14(t，2 H)，4.28(s，4 H)，6.31(s，1 H)，6.96(m，3 H)，7.21(d，2 H)，7.63(d，2 H)，7.91(s，1 H)，8.61(s，1 H)，8.66(s，2 H)，9.19(s，1 H)。 TLC: Rf 0.49 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 1.25 (s, 9 H), 1.80-2.00 (m, 4 H), 2.61 (t, 2 H), 4.14 ( t,2 H), 4.28 (s, 4 H), 6.31 (s, 1 H), 6.96 (m, 3 H), 7.21 (d, 2 H), 7.63 (d, 2 H), 7.91 (s, 1 H), 8.61 (s, 1 H), 8.66 (s, 2 H), 9.19 (s, 1 H).

實施例66-50：1-[1-(2，5-二甲基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 66-50: 1-[1-(2,5-Dimethylphenyl)-3-(2-methyl-2-propyl)-1H-pyrazole-5-yl]-3-( 2-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.70(二氯甲烷：乙酸乙酯：甲醇=8：4：1)；1H-NMR(DMSO-d6)：δ 1.27(s，9 H)，1.93(s，3 H)，2.10-2.23(m，2 H)，2.33(s，3 H)，2.64(t，2 H)，4.05(t，2 H)，6.33(s，1 H)，7.12-7.30(m，5 H)，7.66(d，2 H)，7.88(s，1 H)，8.36(s，1 H)，8.63(s，2 H)，9.07(s，1 H)。 TLC: Rf 0.70 (dichloromethane: ethyl acetate:methanol = 8:4:1); 1 H-NMR (DMSO-d 6 ): δ 1.27 (s, 9 H), 1.93 (s, 3 H), 2.10-2.23 (m, 2 H), 2.33 (s, 3 H), 2.64 (t, 2 H), 4.05 (t, 2 H), 6.33 (s, 1 H), 7.12-7.30 (m, 5 H) ), 7.66 (d, 2 H), 7.88 (s, 1 H), 8.36 (s, 1 H), 8.63 (s, 2 H), 9.07 (s, 1 H).

實施例66-51：1-{1-[3-(2-羥基乙基)苯基]-3-(2-甲基-2-丙基)-1H-吡唑-5-基}-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 66-51:1-{1-[3-(2-Hydroxyethyl)phenyl]-3-(2-methyl-2-propyl)-1H-pyrazole-5-yl}-3 -(2-{4-[2-(2-Sideoxy-1-piperidyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.50(二氯甲烷：乙酸乙酯：甲醇=8：4：1)；1H-NMR(DMSO-d6)：δ 1.27(s，9 H)，1.77-2.00(m，4 H)，2.61(t，2 H)，2.78(t，2 H)，3.55-3.68(m，2 H)，4.07(t，2 H)，4.65(t，1 H)，6.35(s，1 H)，7.17-7.27(m，3 H)，7.28-7.44(m，3 H)，7.65(d，2 H)，7.91(s，1 H)，8.60(s，1 H)，8.64(s，2 H)，9.19(s，1 H)。 TLC: Rf 0.50 (dichloromethane: ethyl acetate:methanol = 8:4:1); 1 H-NMR (DMSO-d 6 ): δ 1.27 (s, 9 H), 1.77-2.00 (m, 4 H) ), 2.61 (t, 2 H), 2.78 (t, 2 H), 3.55-3.68 (m, 2 H), 4.07 (t, 2 H), 4.65 (t, 1 H), 6.35 (s, 1 H) ), 7.17-7.27 (m, 3 H), 7.28-7.44 (m, 3 H), 7.65 (d, 2 H), 7.91 (s, 1 H), 8.60 (s, 1 H), 8.64 (s, 2 H), 9.19 (s, 1 H).

實施例66-52：1-[1-(3，5-二甲基-4-丙氧基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 66-52: 1-[1-(3,5-Dimethyl-4-propoxyphenyl)-3-(2-methyl-2-propyl)-1H-pyrazole-5- 3-(2-{4-[2-(2-Sideoxy-1-piperidyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.80(二氯甲烷：乙酸乙酯：甲醇=8：4：1)；1H-NMR(DMSO-d6)：δ 1.04(t，3 H)，1.25(s，9 H)，1.70-2.00(m，6 H)，2.26(s，6 H)，2.61(t，2 H)，3.73(t，2 H)，4.07(t，2 H)，6.33(s，1 H)，7.13(s，2 H)，7.21(d，2 H)，7.65(d，2 H)，7.91(s，1 H)，8.57(s，1 H)，8.65(s，2 H)，9.17(s，1 H)。 TLC: Rf 0.80 (dichloromethane: ethyl acetate:methanol = 8:4:1); 1 H-NMR (DMSO-d 6 ): δ 1.04 (t, 3 H), 1.25 (s, 9 H), 1.70-2.00 (m, 6 H), 2.26 (s, 6 H), 2.61 (t, 2 H), 3.73 (t, 2 H), 4.07 (t, 2 H), 6.33 (s, 1 H), 7.13(s, 2 H), 7.21 (d, 2 H), 7.65 (d, 2 H), 7.91 (s, 1 H), 8.57 (s, 1 H), 8.65 (s, 2 H), 9.17 ( s, 1 H).

實施例66-53：1-[1-(3-異丙基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 66-53: 1-[1-(3-Isopropylphenyl)-3-(2-methyl-2-propyl)-1H-pyrazol-5-yl]-3-(2- {4-[2-(2-Sideoxy-1-piperidyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.78(二氯甲烷：乙酸乙酯：甲醇=8：4：1)；1H-NMR(DMSO-d6)：δ 1.20(d，6 H)，1.27(s，9 H)，1.78-2.00(m，4 H)，2.61(t，2 H)，2.75-3.00(m，1 H)，4.07(t，2 H)，6.34(s，1 H)，7.20(d，2 H)，7.24-7.46(m，4 H)，7.65(d，2 H)，7.91(s，1 H)，8.59(s，1 H)，8.64(s，2 H)，9.20(s，1 H)。 TLC: Rf 0.78 (dichloromethane: ethyl acetate:methanol = 8:4:1); 1 H-NMR (DMSO-d 6 ): δ 1.20 (d, 6 H), 1.27 (s, 9 H), 1.78-2.00 (m, 4 H), 2.61 (t, 2 H), 2.75-3.00 (m, 1 H), 4.07 (t, 2 H), 6.34 (s, 1 H), 7.20 (d, 2 H) ), 7.24-7.46 (m, 4 H), 7.65 (d, 2 H), 7.91 (s, 1 H), 8.59 (s, 1 H), 8.64 (s, 2 H), 9.20 (s, 1 H) ).

實施例66-54：1-[1-(2，3-二氫-1-苯并呋喃-5-基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Examples 66-54: 1-[1-(2,3-Dihydro-1-benzofuran-5-yl)-3-(2-methyl-2-propyl)-1H-pyrazole-5 -yl]-3-(2-{4-[2-(2-o-oxy-1-piperidyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.65(二氯甲烷：乙酸乙酯：甲醇=8：4：1)；1H-NMR(DMSO-d6)：δ 1.25(s，9 H)，1.78-2.00(m，4 H)，2.61(t，2 H)，3.23(t，2 H)，4.07(t，2 H)，4.59(t，2 H)，6.31(s，1 H)，6.86(d，1 H)，7.13-7.26(m，3 H)，7.28-7.34(m，1 H)，7.65(d，2 H)，7.91(s，1 H)，8.50(s，1 H)，8.65(s，2 H)，9.17(s，1 H)。 TLC: Rf 0.65 (dichloromethane: ethyl acetate:methanol = 8:4:1); 1 H-NMR (DMSO-d 6 ): δ 1.25 (s, 9 H), 1.78-2.00 (m, 4 H) ), 2.61 (t, 2 H), 3.23 (t, 2 H), 4.07 (t, 2 H), 4.59 (t, 2 H), 6.31 (s, 1 H), 6.86 (d, 1 H), 7.13-7.26 (m, 3 H), 7.28-7.34 (m, 1 H), 7.65 (d, 2 H), 7.91 (s, 1 H), 8.50 (s, 1 H), 8.65 (s, 2 H) ), 9.17 (s, 1 H).

實施例66-55：1-[1-(2-氯-6-甲基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 66-55: 1-[1-(2-Chloro-6-methylphenyl)-3-(2-methyl-2-propyl)-1H-pyrazol-5-yl]-3- (2-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.22(甲醇：氯仿=1：19)；1H-NMR(DMSO-d6)：δ 1.25(s，9 H)，1.97(s，3 H)，2.10-2.22(m，2 H)，2.64(t，2 H)，4.05(t，2 H)，6.36(s，1 H)，7.17-7.23(m，2 H)，7.38-7.56(m，3 H)，7.63-7.68(m，2 H)，7.88(s，1 H)，8.45(s，1 H)，8.64(s，2 H)，8.93(s，1 H)。 TLC: Rf 0.22 (methanol: chloroform = 1: 19); 1 H -NMR (DMSO-d 6): δ 1.25 (s, 9 H), 1.97 (s, 3 H), 2.10-2.22 (m, 2 H ), 2.64 (t, 2 H), 4.05 (t, 2 H), 6.36 (s, 1 H), 7.17-7.23 (m, 2 H), 7.38-7.56 (m, 3 H), 7.63-7.68 ( m, 2 H), 7.88 (s, 1 H), 8.45 (s, 1 H), 8.64 (s, 2 H), 8.93 (s, 1 H).

實施例66-56：1-[1-(3-氟-2-甲基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 66-56: 1-[1-(3-Fluoro-2-methylphenyl)-3-(2-methyl-2-propyl)-1H-pyrazole-5-yl]-3- (2-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.32(甲醇：氯仿=1：19)； 1H-NMR(DMSO-d6)：δ 1.26(s，9 H)，1.91(d，3 H)，2.11-2.21(m，2 H)，2.64(t，2 H)，4.05(t，2 H)，6.35(s，1 H)，7.17-7.24(m，3 H)，7.31-7.45(m，2 H)，7.63-7.69(m，2 H)，7.88(s，1 H)，8.46(s，1 H)，8.63(s，2 H)，9.01(s，1 H)。 TLC: Rf 0.32 (methanol: chloroform = 1:19); 1 H-NMR (DMSO-d 6 ): δ 1.26 (s, 9 H), 1.91 (d, 3 H), 2.11-2.21 (m, 2 H) ), 2.64 (t, 2 H), 4.05 (t, 2 H), 6.35 (s, 1 H), 7.17-7.24 (m, 3 H), 7.31-7.45 (m, 2 H), 7.63-7.69 ( m, 2 H), 7.88 (s, 1 H), 8.46 (s, 1 H), 8.63 (s, 2 H), 9.01 (s, 1 H).

實施例66-57：1-[1-(5-氟-2-甲基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 66-57: 1-[1-(5-Fluoro-2-methylphenyl)-3-(2-methyl-2-propyl)-1H-pyrazole-5-yl]-3- (2-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.40(甲醇：氯仿=1：19)；1H-NMR(DMSO-d6)：δ 1.26(s，9 H)，1.96(s，3 H)，2.10-2.21(m，2 H)，2.64(t，2 H)，4.05(t，2 H)，6.34(s，1 H)，7.17-7.23(m，2 H)，7.26-7.34(m，2 H)，7.40-7.47(m，1 H)，7.63-7.68(m，2 H)，7.88(s，1 H)，8.47(s，1 H)，8.63(s，2 H)，9.03(s，1 H)。 TLC: Rf 0.40 (methanol: chloroform = 1: 19); 1 H -NMR (DMSO-d 6): δ 1.26 (s, 9 H), 1.96 (s, 3 H), 2.10-2.21 (m, 2 H ), 2.64 (t, 2 H), 4.05 (t, 2 H), 6.34 (s, 1 H), 7.17-7.23 (m, 2 H), 7.26-7.34 (m, 2 H), 7.40-7.47 ( m,1 H), 7.63-7.68 (m, 2 H), 7.88 (s, 1 H), 8.47 (s, 1 H), 8.63 (s, 2 H), 9.03 (s, 1 H).

實施例66-58：1-[1-(2-乙基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 66-58: 1-[1-(2-Ethylphenyl)-3-(2-methyl-2-propyl)-1H-pyrazol-5-yl]-3-(2-{ 4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.40(甲醇：氯仿=1：19)；1H-NMR(DMSO-d6)：δ 1.00(t，3 H)，1.25(s，9 H)，2.11-2.22(m，2 H)，2.31(q，2 H)，2.64(t，2 H)，4.05(t，2 H)，6.34(s，1 H)，7.18-7.23(m，2 H)，7.28-7.51(m，4 H)，7.62-7.68(m，2 H)，7.88(s，1 H)，8.36(s，1 H)，8.62(s，2 H)，9.07(s，1 H)。 TLC: Rf 0.40 (methanol: chloroform = 1: 19); 1 H -NMR (DMSO-d 6): δ 1.00 (t, 3 H), 1.25 (s, 9 H), 2.11-2.22 (m, 2 H ), 2.31 (q, 2 H), 2.64 (t, 2 H), 4.05 (t, 2 H), 6.34 (s, 1 H), 7.18-7.23 (m, 2 H), 7.28-7.51 (m, 4 H), 7.62-7.68 (m, 2 H), 7.88 (s, 1 H), 8.36 (s, 1 H), 8.62 (s, 2 H), 9.07 (s, 1 H).

實施例66-59：1-[1-(2-甲基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-氮呯基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Examples 66-59: 1-[1-(2-Methylphenyl)-3-(2-methyl-2-propyl)-1H-pyrazol-5-yl]-3-(2-{ 4-[2-(2-Sideoxy-1-indolyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.79(乙酸乙酯)； 1H-NMR(DMSO-d6)：δ 1.26(s，9 H)，1.73(m，6 H)，1.99(s，3 H)，2.83(m，2 H)，4.45(t，2 H)，6.34(s，1 H)，7.20(d，2 H)，7.28-7.41(m，4 H)，7.64(d，2 H)，7.86(s，1 H)8.38(s，1 H)，8.63(s，2 H)，9.06(s，1 H)。 TLC: Rf 0.79 (ethyl acetate); 1 H-NMR (DMSO -d 6): δ 1.26 (s, 9 H), 1.73 (m, 6 H), 1.99 (s, 3 H), 2.83 (m, 2 H), 4.45 (t, 2 H), 6.34 (s, 1 H), 7.20 (d, 2 H), 7.28-7.41 (m, 4 H), 7.64 (d, 2 H), 7.86 (s, 1 H) 8.38 (s, 1 H), 8.63 (s, 2 H), 9.06 (s, 1 H).

實施例66-60：1-[1-(2-氯苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 66-60: 1-[1-(2-Chlorophenyl)-3-(2-methyl-2-propyl)-1H-pyrazol-5-yl]-3-(2-{4 -[2-(2-Sideoxy-1-piperidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.29(己烷：乙酸乙酯=1：4)；1H-NMR(DMSO-d6)：δ 1.25(s，9 H)，1.78-1.98(m，4 H)，2.60(t，2 H)，4.06(t，2 H)，6.35(s，1 H)，7.20(d，2 H)，7.51-7.72(m，6 H)，7.90(s，1 H)，8.51(s，1 H)，8.63(s，2 H)，8.99(s，1 H)。 TLC: Rf 0.29 (hexane: ethyl acetate = 1 : 4); 1 H-NMR (DMSO-d 6 ): δ 1.25 (s, 9 H), 1.78-1.98 (m, 4 H), 2.60 (t) , 2 H), 4.06 (t, 2 H), 6.35 (s, 1 H), 7.20 (d, 2 H), 7.51-7.72 (m, 6 H), 7.90 (s, 1 H), 8.51 (s) , 1 H), 8.63 (s, 2 H), 8.99 (s, 1 H).

實施例66-61：1-{3-(2-甲基-2-丙基)-1-[3-(三氟甲基)苯基]-1H-吡唑-5-基}-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 66-61:1-{3-(2-Methyl-2-propyl)-1-[3-(trifluoromethyl)phenyl]-1H-pyrazole-5-yl}-3- (2-{4-[2-(2-Sideoxy-1-piperidyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.38(己烷：乙酸乙酯=1：2)；1H-NMR(DMSO-d6)：δ 1.28(s，9 H)，1.77-1.98(m，4 H)，2.60(t，2 H)，4.06(t，2 H)，6.38(s，1 H)，7.20(d，2 H)，7.65(d，2 H)，7.70-7.76(m，2 H)，7.82-7.89(m，2 H)，7.90(s，1 H)，8.61(s，2 H)，8.74(s，1 H)，9.22(s，1 H)。 TLC: Rf 0.38 (hexane: ethyl acetate = 1:2); 1 H-NMR (DMSO-d 6 ): δ 1.28 (s, 9 H), 1.77-1.98 (m, 4 H), 2.60 (t) , 2 H), 4.06 (t, 2 H), 6.38 (s, 1 H), 7.20 (d, 2 H), 7.65 (d, 2 H), 7.70-7.76 (m, 2 H), 7.82-7.89 (m, 2 H), 7.90 (s, 1 H), 8.61 (s, 2 H), 8.74 (s, 1 H), 9.22 (s, 1 H).

實施例66-62：1-[1-(3-乙基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 66-62: 1-[1-(3-Ethylphenyl)-3-(2-methyl-2-propyl)-1H-pyrazol-5-yl]-3-(2-{ 4-[2-(2-Sideoxy-1-piperidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.39(己烷：乙酸乙酯=1：2)；1H-NMR(DMSO-d6)：δ 1.18(t，3 H)，1.26(s，9 H)，1.77-1.98(m， 4 H)，2.56-2.72(m，4 H)，4.06(t，2 H)，6.34(s，1 H)，7.17-7.45(m，6 H)，7.64(d，2 H)，7.90(s，1 H)，8.59(s，1 H)，8.63(s，2 H)，9.19(s，1 H)。 TLC: Rf 0.39 (hexane: ethyl acetate = 1: 2); 1 H -NMR (DMSO-d 6): δ 1.18 (t, 3 H), 1.26 (s, 9 H), 1.77-1.98 (m , 4 H), 2.56-2.72 (m, 4 H), 4.06 (t, 2 H), 6.34 (s, 1 H), 7.17-7.45 (m, 6 H), 7.64 (d, 2 H), 7.90 (s, 1 H), 8.59 (s, 1 H), 8.63 (s, 2 H), 9.19 (s, 1 H).

實施例66-63：1-[1-(2-氯-4-氟苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Examples 66-63: 1-[1-(2-Chloro-4-fluorophenyl)-3-(2-methyl-2-propyl)-1H-pyrazol-5-yl]-3-( 2-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.65(二氯甲烷：乙酸乙酯：甲醇=8：4：1)；1H-NMR(DMSO-d6)：δ 1.25(s，9 H)，2.10-2.23(m，2 H)，2.64(t，2 H)，4.05(t，2 H)，6.35(s，1 H)，7.21(d，2 H)，7.37-7.47(m，1 H)，7.60-7.70(m，3 H)，7.71-7.78(m，1 H)，7.89(s，1 H)，8.55(s，1 H)，8.65(s，2 H)，8.93(s，1 H)。 TLC: Rf 0.65 (dichloromethane: ethyl acetate:methanol = 8:4:1); 1 H-NMR (DMSO-d 6 ): δ 1.25 (s, 9 H), 2.10-2.23 (m, 2 H) ), 2.64 (t, 2 H), 4.05 (t, 2 H), 6.35 (s, 1 H), 7.21 (d, 2 H), 7.37-7.47 (m, 1 H), 7.60-7.70 (m, 3 H), 7.71-7.78 (m, 1 H), 7.89 (s, 1 H), 8.55 (s, 1 H), 8.65 (s, 2 H), 8.93 (s, 1 H).

實施例66-64：1-[1-(4-氯-2-甲基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Examples 66-64: 1-[1-(4-Chloro-2-methylphenyl)-3-(2-methyl-2-propyl)-1H-pyrazol-5-yl]-3- (2-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.61(二氯甲烷：乙酸乙酯：甲醇=8：4：1)；1H-NMR(DMSO-d6)：δ 1.25(s，9 H)，1.99(s，3 H)，2.16(t，2 H)，2.64(t，2 H)，4.05(t，2 H)，6.34(s，1 H)，7.21(d，2 H)，7.33-7.45(m，2 H)，7.50-7.56(m，1 H)，7.66(d，2 H)，7.89(s，1 H)，8.44(s，1 H)，8.63(s，2 H)，9.00(s，1 H)。 TLC: Rf 0.61 (dichloromethane: ethyl acetate: methanol = 8: 4: 1); 1 H-NMR (DMSO-d 6): δ 1.25 (s, 9 H), 1.99 (s, 3 H), 2.16(t, 2 H), 2.64(t, 2 H), 4.05(t, 2 H), 6.34(s, 1 H), 7.21(d, 2 H), 7.33-7.45(m, 2 H), 7.50-7.56 (m, 1 H), 7.66 (d, 2 H), 7.89 (s, 1 H), 8.44 (s, 1 H), 8.63 (s, 2 H), 9.00 (s, 1 H).

實施例66-65：1-[1-(3-甲氧基-2，4-二甲基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 66-65: 1-[1-(3-Methoxy-2,4-dimethylphenyl)-3-(2-methyl-2-propyl)-1H-pyrazole-5- 3-(2-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.59(二氯甲烷：乙酸乙酯：甲醇=8：4：1)；1H-NMR(DMSO-d6)：δ 1.25(s，9 H)，1.85(s，3 H)，2.10-2.23(m， 2 H)，2.31(s，3 H)，2.64(t，2 H)，3.71(s，3 H)，4.05(t，2 H)，6.33(s，1 H)，7.02(d，1 H)，7.15-7.26(m，3 H)，7.66(d，2 H)，7.89(s，1 H)，8.34(s，1 H)，8.63(s，2 H)，9.06(s，1 H)。 TLC: Rf 0.59 (dichloromethane: ethyl acetate:methanol = 8:4:1); 1 H-NMR (DMSO-d 6 ): δ 1.25 (s, 9 H), 1.85 (s, 3 H), 2.10-2.23 (m, 2 H), 2.31 (s, 3 H), 2.64 (t, 2 H), 3.71 (s, 3 H), 4.05 (t, 2 H), 6.33 (s, 1 H), 7.02 (d, 1 H), 7.15-7.26 (m, 3 H), 7.66 (d, 2 H), 7.89 (s, 1 H), 8.34 (s, 1 H), 8.63 (s, 2 H), 9.06 (s, 1 H).

實施例66-66：1-[1-(2-甲氧基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 66-66: 1-[1-(2-Methoxyphenyl)-3-(2-methyl-2-propyl)-1H-pyrazol-5-yl]-3-(2- {4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.53(二氯甲烷：乙酸乙酯：甲醇=8：4：1)；1H-NMR(DMSO-d6)：δ 1.25(s，9 H)，2.10-2.24(m，2 H)，2.64(t，2 H)，3.79(s，3 H)，4.05(t，2 H)，6.32(s，1 H)，7.09(td，1 H)，7.20(d，2 H)，7.26(d，1 H)，7.32(dd，1 H)，7.49(td，1 H)，7.66(d，2 H)，7.88(s，1 H)，8.17(s，1 H)，8.64(s，2 H)，9.23(s，1 H)。 TLC: Rf 0.53 (dichloromethane: ethyl acetate:methanol = 8:4:1); 1 H-NMR (DMSO-d 6 ): δ 1.25 (s, 9 H), 2.10-2.24 (m, 2 H) ), 2.64 (t, 2 H), 3.79 (s, 3 H), 4.05 (t, 2 H), 6.32 (s, 1 H), 7.09 (td, 1 H), 7.20 (d, 2 H), 7.26 (d, 1 H), 7.32 (dd, 1 H), 7.49 (td, 1 H), 7.66 (d, 2 H), 7.88 (s, 1 H), 8.17 (s, 1 H), 8.64 ( s, 2 H), 9.23 (s, 1 H).

實施例66-67：1-[1-(2-氟-5-甲基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 66-67: 1-[1-(2-Fluoro-5-methylphenyl)-3-(2-methyl-2-propyl)-1H-pyrazol-5-yl]-3- (2-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.61(二氯甲烷：乙酸乙酯：甲醇=8：4：1)；1H-NMR(DMSO-d6)：δ 1.25(s，9 H)，2.10-2.23(m，2 H)，2.35(s，3 H)，2.64(t，2 H)，4.05(t，2 H)，6.35(s，1 H)，7.20(d，2 H)，7.31-7.37(m，3 H)，7.66(d，2 H)，7.88(s，1 H)，8.59(s，1 H)，8.64(s，2 H)，9.04(s，1 H)。 TLC: Rf 0.61 (dichloromethane: ethyl acetate:methanol = 8:4:1); 1 H-NMR (DMSO-d 6 ): δ 1.25 (s, 9 H), 2.10-2.23 (m, 2 H) ), 2.35 (s, 3 H), 2.64 (t, 2 H), 4.05 (t, 2 H), 6.35 (s, 1 H), 7.20 (d, 2 H), 7.31-7.37 (m, 3 H) ), 7.66 (d, 2 H), 7.88 (s, 1 H), 8.59 (s, 1 H), 8.64 (s, 2 H), 9.04 (s, 1 H).

實施例66-68：1-[1-(2-氯-5-甲基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 66-68: 1-[1-(2-Chloro-5-methylphenyl)-3-(2-methyl-2-propyl)-1H-pyrazol-5-yl]-3- (2-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.60(二氯甲烷：乙酸乙酯：甲醇=8：4：1)； 1H-NMR(DMSO-d6)：δ 1.25(s，9 H)，2.10-2.23(m，2 H)，2.37(s，3 H)，2.64(t，2 H)，4.05(t，2 H)，6.34(s，1 H)，7.21(d，2 H)，7.35-7.43(m，2 H)，7.54-7.60(m，1 H)，7.66(d，2 H)，7.89(s，1 H)，8.49(s，1 H)，8.65(s，2 H)，9.00(s，1 H)。 TLC: Rf 0.60 (dichloromethane: ethyl acetate:methanol = 8:4:1); 1 H-NMR (DMSO-d 6 ): δ 1.25 (s, 9 H), 2.10-2.23 (m, 2 H) ), 2.37 (s, 3 H), 2.64 (t, 2 H), 4.05 (t, 2 H), 6.34 (s, 1 H), 7.21 (d, 2 H), 7.35-7.43 (m, 2 H) ), 7.54-7.60 (m, 1 H), 7.66 (d, 2 H), 7.89 (s, 1 H), 8.49 (s, 1 H), 8.65 (s, 2 H), 9.00 (s, 1 H) ).

實施例66-69：1-[1-(2-氟-4-甲基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Examples 66-69: 1-[1-(2-Fluoro-4-methylphenyl)-3-(2-methyl-2-propyl)-1H-pyrazole-5-yl]-3- (2-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.60(二氯甲烷：乙酸乙酯：甲醇=8：4：1)；1H-NMR(DMSO-d6)：δ 1.25(s，9 H)，2.10-2.23(m，2 H)，2.40(s，3 H)，2.64(t，2 H)，4.05(t，2 H)，6.35(s，1 H)，7.15-7.25(m，3 H)，7.25-7.35(m，1 H)，7.39(t，1 H)，7.66(d，2 H)，7.89(s，1 H)，8.56(s，1 H)，8.65(s，2 H)，9.05(s，1 H)。 TLC: Rf 0.60 (dichloromethane: ethyl acetate:methanol = 8:4:1); 1 H-NMR (DMSO-d 6 ): δ 1.25 (s, 9 H), 2.10-2.23 (m, 2 H) ), 2.40 (s, 3 H), 2.64 (t, 2 H), 4.05 (t, 2 H), 6.35 (s, 1 H), 7.15-7.25 (m, 3 H), 7.25-7.35 (m, 1 H), 7.39 (t, 1 H), 7.66 (d, 2 H), 7.89 (s, 1 H), 8.56 (s, 1 H), 8.65 (s, 2 H), 9.05 (s, 1 H) ).

實施例66-70：1-[1-(3-氟-2，4-二甲基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 66-70: 1-[1-(3-Fluoro-2,4-dimethylphenyl)-3-(2-methyl-2-propyl)-1H-pyrazol-5-yl] -3-(2-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.62(二氯甲烷：乙酸乙酯：甲醇=8：4：1)；1H-NMR(DMSO-d6)：δ 1.25(s，9 H)，1.87(d，3 H)，2.10-2.23(m，2 H)，2.30(d，3 H)，2.64(t，2 H)，4.05(t，2 H)，6.34(s，1 H)，7.10(d，1 H)，7.20(d，2 H)，7.27(t，1 H)，7.66(d，2 H)，7.88(s，1 H)，8.40(s，1 H)，8.63(s，2 H)，9.01(s，1 H)。 TLC: Rf 0.62 (dichloromethane: ethyl acetate: methanol = 8: 4: 1); 1 H-NMR (DMSO-d 6): δ 1.25 (s, 9 H), 1.87 (d, 3 H), 2.10-2.23 (m, 2 H), 2.30 (d, 3 H), 2.64 (t, 2 H), 4.05 (t, 2 H), 6.34 (s, 1 H), 7.10 (d, 1 H), 7.20(d,2 H), 7.27(t,1 H), 7.66(d,2 H), 7.88(s,1 H), 8.40(s,1 H), 8.63(s,2 H),9.01 ( s, 1 H).

實施例66-71：1-[1-(2-氯-4-甲基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 66-71:1-[1-(2-Chloro-4-methylphenyl)-3-(2-methyl-2-propyl)-1H-pyrazole-5-yl]-3- (2-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.61(二氯甲烷：乙酸乙酯：甲醇=8：4：1)； 1H-NMR(DMSO-d6)：δ 1.25(s，9 H)，2.10-2.23(m，2 H)，2.40(s，3 H)，2.64(t，2 H)，4.05(t，2 H)，6.33(s，1 H)，7.20(d，2 H)，7.30-7.36(m，1 H)，7.42(d，1 H)，7.53(s，1 H)，7.66(d，2 H)，7.89(s，1 H)，8.46(s，1 H)，8.64(s，2 H)，9.01(s，1 H)。 TLC: Rf 0.61 (dichloromethane: ethyl acetate:methanol = 8:4:1); 1 H-NMR (DMSO-d 6 ): δ 1.25 (s, 9 H), 2.10-2.23 (m, 2 H) ), 2.40 (s, 3 H), 2.64 (t, 2 H), 4.05 (t, 2 H), 6.33 (s, 1 H), 7.20 (d, 2 H), 7.30-7.36 (m, 1 H) ), 7.42 (d, 1 H), 7.53 (s, 1 H), 7.66 (d, 2 H), 7.89 (s, 1 H), 8.46 (s, 1 H), 8.64 (s, 2 H), 9.01(s, 1 H).

實施例66-72：4-[3-(2-甲基-2-丙基)-5-{[(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)胺基甲醯基]胺基}-1H-吡唑-1-基]苯磺醯胺 Example 66-72: 4-[3-(2-Methyl-2-propyl)-5-{[(2-{4-[2-(2-Sideoxy-1-pyrrolidinyl)- 1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)aminomethylindenyl]amino}-1H-pyrazol-1-yl]benzenesulfonamide

TLC：Rf 0.48(二氯甲烷：乙酸乙酯：甲醇=8：4：1)；1H-NMR(DMSO-d6)：δ 1.28(s，9 H)，2.10-2.23(m，2 H)，2.64(t，2 H)，4.05(t，2 H)，6.40(s，1 H)，7.21(d，2 H)，7.45(s，2 H)，7.67(d，2 H)，7.73(d，2 H)，7.88-7.96(m，3 H)，8.66(s，2 H)，8.79(s，1 H)，9.23(s，1 H)。 TLC: Rf 0.48 (dichloromethane: ethyl acetate:methanol = 8:4:1); 1 H-NMR (DMSO-d 6 ): δ 1.28 (s, 9 H), 2.10-2.23 (m, 2 H) ), 2.64 (t, 2 H), 4.05 (t, 2 H), 6.40 (s, 1 H), 7.21 (d, 2 H), 7.45 (s, 2 H), 7.67 (d, 2 H), 7.73 (d, 2 H), 7.88-7.96 (m, 3 H), 8.66 (s, 2 H), 8.79 (s, 1 H), 9.23 (s, 1 H).

實施例67-1，2 Example 67-1, 2

使用(2-甲基苯基)肼鹽酸鹽替代(3，4-二甲基苯基)肼鹽酸鹽，使用2-氯-5-硝基吡啶或2-氯-3-甲基-5-硝基吡啶替代2-氯-5-硝基嘧啶，使用1-(5-溴噻唑-2-基)吡咯啶-2-酮替代實施例18製造之化合物，進行與實施例62→實施例63→實施例12→實施例13→實施例9→實施例20→實施例21相同之操作，獲得具有以下物性值之本發明化合物。 Substituting (2-methylphenyl)phosphonium hydrochloride for (3,4-dimethylphenyl)phosphonium hydrochloride using 2-chloro-5-nitropyridine or 2-chloro-3-methyl- Substituting 5-nitropyridine for 2-chloro-5-nitropyrimidine, using 1-(5-bromothiazol-2-yl)pyrrolidin-2-one in place of the compound produced in Example 18, and carrying out Example 62→ Example 63 → Example 12 → Example 13 → Example 9 → Example 20 → Example 21 The same procedure as in Example 21 was carried out to obtain a compound of the present invention having the following property values.

實施例67-1：1-[1-(2-甲基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(6-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)脲 Example 67-1:1-[1-(2-Methylphenyl)-3-(2-methyl-2-propyl)-1H-pyrazole-5-yl]-3-(6-{ 4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-3-pyridyl)urea

TLC：Rf 0.49(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 1.25(s，9 H)，1.99(s，3 H)，2.16(m，2 H)，2.63(t，2 H)，4.04(t，2 H)，6.33(s，1 H)，7.01(d，1 H)，7.11(d，2 H)，7.31-7.44(m，4 H)，7.63(d，2 H)，7.86(s，1 H)，7.95(dd，1 H)，8.09(d，1 H)，8.23(s，1 H)，9.00(s，1 H)。 TLC: Rf 0.49 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 1.25 (s, 9 H), 1.99 (s, 3 H), 2.16 (m, 2 H), 2.63 (t, 2 H), 4.04 (t, 2 H), 6.33 (s, 1 H), 7.01 (d, 1 H), 7.11 (d, 2 H), 7.31-7.44 (m, 4 H), 7.63 (d, 2 H), 7.86 (s, 1 H), 7.95 (dd, 1 H), 8.09 (d, 1 H), 8.23 (s, 1 H), 9.00 (s, 1 H).

實施例67-2：1-(5-甲基-6-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)-3-[1-(2-甲基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]脲 Example 67-2: 1-(5-Methyl-6-{4-[2-(2-o-oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy} -3-pyridyl)-3-[1-(2-methylphenyl)-3-(2-methyl-2-propyl)-1H-pyrazol-5-yl]urea

TLC：Rf 0.53(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 1.25(s，9 H)，1.99(s，3 H)，2.16(m，2 H)，2.25(s，3 H)，2.63(t，2 H)，4.04(t，2 H)，6.34(s，1 H)，7.06(d，2 H)，7.31-7.44(m，4 H)，7.61(d，2 H)，7.84(s，1 H)，7.86(s，1 H)，7.88(s，1 H)，8.22(s，1 H)，8.94(s，1 H)。 TLC: Rf 0.53 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 1.25 (s, 9 H), 1.99 (s, 3 H), 2.16 (m, 2 H), 2.25 (s, 3 H), 2.63 (t, 2 H), 4.04 (t, 2 H), 6.34 (s, 1 H), 7.06 (d, 2 H), 7.31-7.44 (m, 4 H), 7.61 (d, 2 H), 7.84 (s, 1 H), 7.86 (s, 1 H), 7.88 (s, 1 H), 8.22 (s, 1 H), 8.94 (s, 1 H).

實施例68：3-(第三丁基)-1-(1-甲基-1H-吲哚-5-基)-1H-吡唑-5-胺 Example 68: 3-(Tert-butyl)-1-(1-methyl-1H-indol-5-yl)-1H-pyrazole-5-amine

於二甲基甲醯胺(8mL)及吡啶(0.47mL)之混合溶劑中加入3-胺基-5-第三丁基吡唑(810mg)、N-甲基吲哚-5-硼酸(780mg)、乙酸銅(Ⅱ)(790mg)及分子篩(400mg)。反應混合物於室溫攪拌整晚。於反應混合物中加入10%氨水，將反應混合物以Celite(註冊商標)過濾。濾液中加入乙酸乙酯，分液。獲得之有機層以飽和食鹽水洗淨，以無水硫酸鈉乾燥。獲得之殘渣以矽膠管柱層析儀(己烷：乙 酸乙酯=7：3→1：1→1：4)精製，獲得具有以下物性值之標題化合物(577mg)。 3-Amino-5-t-butylpyrazole (810 mg), N-methylindole-5-boric acid (780 mg) was added to a mixed solvent of dimethylformamide (8 mL) and pyridine (0.47 mL). ), copper (II) acetate (790 mg) and molecular sieves (400 mg). The reaction mixture was stirred overnight at room temperature. 10% aqueous ammonia was added to the reaction mixture, and the reaction mixture was filtered through Celite (registered trademark). Ethyl acetate was added to the filtrate, and the mixture was separated. The obtained organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. Obtained residue by gel column chromatography (hexane: B Purification with ethyl acetate = 7:3 - 1:1 - 1 : 4) gave the title compound (577 mg).

TLC：Rf 0.29(己烷：乙酸乙酯=2：1)。 TLC: Rf 0.29 (hexane: ethyl acetate = 2:1).

實施例69：2，2，2-三氯乙基(3-(第三丁基)-1-(1-甲基-1H-吲哚-5-基)-1H-吡唑-5-基)胺基甲酸酯 Example 69: 2,2,2-trichloroethyl (3-(t-butyl)-1-(1-methyl-1H-indol-5-yl)-1H-pyrazole-5-yl Urethane

使用實施例68製造之化合物替代實施例7製造之化合物，進行與實施例8相同之操作，獲得具有以下物性值之標題化合物。 The compound produced in Example 68 was used in place of the compound produced in Example 7, and the same procedure as in Example 8 was carried out to obtain the title compound.

TLC：Rf 0.43(己烷：乙酸乙酯=2：1)。 TLC: Rf 0.43 (hexane: ethyl acetate = 2:1).

實施例70：1-[1-(1-甲基-1H-吲哚-5-基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 70: 1-[1-(1-Methyl-1H-indol-5-yl)-3-(2-methyl-2-propyl)-1H-pyrazol-5-yl]-3 -(2-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

使用實施例69製造之化合物替代實施例16製造之化合物，使用1-(5-溴噻唑-2-基)吡咯啶-2-酮替代實施例18製造之化合物，進行與實施例19→實施例20→實施例21相同之操作，獲得具有以下物性值之本發明化合物。 The compound produced in Example 69 was used in place of the compound produced in Example 16, and the compound produced in Example 18 was replaced with 1-(5-bromothiazol-2-yl)pyrrolidin-2-one, and Example 19→Example was carried out. 20 → The same operation as in Example 21 was carried out to obtain a compound of the present invention having the following property values.

TLC：Rf 0.50(二氯甲烷：乙酸乙酯：甲醇=8：4：1)；1H-NMR(DMSO-d6)：δ 1.27(s，9 H)，2.12-2.23(m，2 H)，2.64(t，2 H)，3.83(s，3 H)，4.05(t，2 H)，6.34(s，1 H)，6.52(d，1 H)，7.17-7.24(m，3 H)，7.44(d，1 H)，7.56(d，1 H)，7.61(d，1 H)， 7.66(d，2 H)，7.89(s，1 H)，8.47(s，1 H)，8.63(s，2 H)，9.18(s，1 H)。 TLC: Rf 0.50 (dichloromethane: ethyl acetate:methanol = 8:4:1); 1 H-NMR (DMSO-d 6 ): δ 1.27 (s, 9 H), 2.12 - 2.23 (m, 2 H) ), 2.64 (t, 2 H), 3.83 (s, 3 H), 4.05 (t, 2 H), 6.34 (s, 1 H), 6.52 (d, 1 H), 7.17-7.24 (m, 3 H ), 7.44 (d, 1 H), 7.56 (d, 1 H), 7.61 (d, 1 H), 7.66 (d, 2 H), 7.89 (s, 1 H), 8.47 (s, 1 H), 8.63 (s, 2 H), 9.18 (s, 1 H).

實施例71：1-[1-(1-甲基-1H-吲唑-5-基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 71:1-[1-(1-Methyl-1H-indazol-5-yl)-3-(2-methyl-2-propyl)-1H-pyrazole-5-yl]-3 -(2-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

使用(1-甲基-1H-吲唑-5-基)硼酸替代(1-甲基-1H-吲哚-5-基)硼酸，使用1-(5-溴噻唑-2-基)吡咯啶-2-酮替代實施例18製造之化合物，進行與實施例68→實施例69→實施例19→實施例20→實施例21相同之操作，獲得具有以下物性值之本發明化合物。 Substituting (1-methyl-1H-indazol-5-yl)boronic acid for (1-methyl-1H-indol-5-yl)boronic acid using 1-(5-bromothiazol-2-yl)pyrrolidine The compound produced in the same manner as in Example 68 → Example 69 → Example 19 → Example 20 → Example 21 was subjected to the same procedure as in Example 18 to obtain a compound of the present invention having the following properties.

TLC：Rf 0.41(乙酸乙酯：甲醇=19：1)；1H-NMR(DMSO-d6)：δ 9.14(s，1 H)，8.63(s，2 H)，8.57(s，1 H)，8.14(d，1 H)，7.89(s，1 H)，7.86(d，1 H)，7.78(d，1H)，7.62-7.70(m，2 H)，7.49(dd，1 H)，7.16-7.25(m，2 H)，6.37(s，1 H)，4.10(s，3 H)，4.01-4.09(m，2 H)，2.60-2.69(m，2H)，2.10-2.24(m，2H)，1.29(s，9H)。 TLC: Rf 0.41 (ethyl acetate:methanol = 19:1); 1 H-NMR (DMSO-d 6 ): δ 9.14 (s, 1 H), 8.63 (s, 2 H), 8.57 (s, 1 H) ), 8.14 (d, 1 H), 7.89 (s, 1 H), 7.86 (d, 1 H), 7.78 (d, 1H), 7.62-7.70 (m, 2 H), 7.49 (dd, 1 H) , 7.16-7.25 (m, 2 H), 6.37 (s, 1 H), 4.10 (s, 3 H), 4.01-4.09 (m, 2 H), 2.60-2.69 (m, 2H), 2.10-2.24 ( m, 2H), 1.29 (s, 9H).

實施例72 Example 72

使用相當之腈衍生物替代三甲基乙醯基乙腈，使用(3，4-二甲基苯基)肼鹽酸鹽、或使用相當之肼衍生物替代(3，4-二甲基苯基)肼鹽酸鹽，使用相當之5-溴噻唑衍生物替代實施例18製造之 化合物，進行與實施例62→實施例63→實施例19→實施例20→實施例21相同之操作，獲得具有以下物性值之本發明化合物。 Replace the trimethylacetamidoacetonitrile with a nitrile derivative, use (3,4-dimethylphenyl)phosphonium hydrochloride, or replace it with a comparable anthracene derivative (3,4-dimethylphenyl) Hydrazine hydrochloride, using an equivalent 5-bromothiazole derivative instead of the example 18 The compound was subjected to the same operation as in Example 62 ?? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ?

實施例72-1：1-[1-(2-甲基苯基)-3-(三氟甲基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 72-1:1-[1-(2-Methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl]-3-(2-{4-[2- (2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.53(二氯甲烷：乙酸乙酯：甲醇=8：4：1)；1H-NMR(DMSO-d6)：δ 2.01(s，3 H)，2.10-2.24(m，2 H)，2.64(t，2 H)，4.04(t，2 H)，6.85(s，1 H)，7.21(d，2 H)，7.40-7.57(m，4 H)，7.66(d，2 H)，7.89(s，1 H)，8.63(s，2 H)，8.82(s，1 H)，9.13(s，1 H)。 TLC: Rf 0.53 (dichloromethane: ethyl acetate:methanol = 8:4:1); 1 H-NMR (DMSO-d 6 ): δ 2.01 (s, 3 H), 2.10-2.24 (m, 2 H) ), 2.64 (t, 2 H), 4.04 (t, 2 H), 6.85 (s, 1 H), 7.21 (d, 2 H), 7.40-7.57 (m, 4 H), 7.66 (d, 2 H) ), 7.89 (s, 1 H), 8.63 (s, 2 H), 8.82 (s, 1 H), 9.13 (s, 1 H).

實施例72-2：1-[1-(3，4-二甲基苯基)-3-(三氟甲基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 72-2: 1-[1-(3,4-Dimethylphenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl]-3-(2-{4- [2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.54(二氯甲烷：乙酸乙酯：甲醇=8：4：1)；1H-NMR(DMSO-d6)：δ 2.10-2.24(m，2 H)，2.30(s，6 H)，2.64(t，2 H)，4.05(t，2 H)，6.85(s，1 H)，7.21(d，2 H)，7.25-7.40(m，3 H)，7.67(d，2 H)，7.89(s，1 H)，8.65(s，2 H)，8.91(s，1 H)，9.27(s，1 H)。 TLC: Rf 0.54 (dichloromethane: ethyl acetate:methanol = 8:4:1); 1 H-NMR (DMSO-d 6 ): δ 2.10-2.24 (m, 2 H), 2.30 (s, 6 H) ), 2.64 (t, 2 H), 4.05 (t, 2 H), 6.85 (s, 1 H), 7.21 (d, 2 H), 7.25-7.40 (m, 3 H), 7.67 (d, 2 H) ), 7.89 (s, 1 H), 8.65 (s, 2 H), 8.91 (s, 1 H), 9.27 (s, 1 H).

實施例72-3：1-[3-(1，1-二氟乙基)-1-(2-甲基苯基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5- 嘧啶基)脲 Example 72-3: 1-[3-(1,1-Difluoroethyl)-1-(2-methylphenyl)-1H-pyrazole-5-yl]-3-(2-{4 -[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5- Pyrimidinyl urea

TLC：Rf 0.51(二氯甲烷：乙酸乙酯：甲醇=8：4：1)；1H-NMR(DMSO-d6)：δ 1.97(t，3 H)，2.00(s，3 H)，2.10-2.24(m，2 H)，2.63(t，2 H)，4.04(t，2 H)，6.64(s，1 H)，7.20(d，2 H)，7.36-7.54(m，4 H)，7.65(d，2 H)，7.88(s，1 H)，8.62(s，2 H)，8.65(s，1 H)，9.09(s，1 H)。 TLC: Rf 0.51 (dichloromethane: ethyl acetate: methanol = 8: 4: 1); 1 H-NMR (DMSO-d 6): δ 1.97 (t, 3 H), 2.00 (s, 3 H), 2.10-2.24 (m, 2 H), 2.63 (t, 2 H), 4.04 (t, 2 H), 6.64 (s, 1 H), 7.20 (d, 2 H), 7.36-7.54 (m, 4 H) ), 7.65 (d, 2 H), 7.88 (s, 1 H), 8.62 (s, 2 H), 8.65 (s, 1 H), 9.09 (s, 1 H).

實施例72-4：1-[1-(4-氟苯基)-3-(三氟甲基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 72-4: 1-[1-(4-Fluorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl]-3-(2-{4-[2-( 2-sided oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.59(二氯甲烷：乙酸乙酯：甲醇=8：4：1)；1H-NMR(DMSO-d6)：δ 2.10-2.24(m，2 H)，2.64(t，2 H)，4.05(t，2 H)，6.88(s，1 H)，7.21(d，2 H)，7.45(t，2 H)，7.60-7.72(m，4 H)，7.89(s，1 H)，8.65(s，2 H)，8.97(s，1 H)，9.24(s，1 H)。 TLC: Rf 0.59 (dichloromethane: ethyl acetate: methanol = 8: 4: 1); 1 H-NMR (DMSO-d 6): δ 2.10-2.24 (m, 2 H), 2.64 (t, 2 H ), 4.05 (t, 2 H), 6.88 (s, 1 H), 7.21 (d, 2 H), 7.45 (t, 2 H), 7.60-7.72 (m, 4 H), 7.89 (s, 1 H) ), 8.65 (s, 2 H), 8.97 (s, 1 H), 9.24 (s, 1 H).

實施例72-5：1-[1-(2-甲基苯基)-3-(三氟甲基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 72-5: 1-[1-(2-Methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl]-3-(2-{4-[2- (2-Sideoxy-1-piperidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.34(己烷：乙酸乙酯=1：4)；1H-NMR(DMSO-d6)：δ 1.83-1.99(m，4 H)，2.01(s，3 H)，2.61(t，2 H)，4.07(t，2 H)，6.85(s，1 H)，7.21(d，2 H)，7.43-7.64(m，4 H)，7.66(d，2 H)，7.91(s，1 H)，8.64(s，2 H)，8.21(s，1 H)， 9.13(s，1 H)。 TLC: Rf 0.34 (hexane: ethyl acetate = 1 : 4); 1 H-NMR (DMSO-d 6 ): δ 1.83-1.99 (m, 4 H), 2.01 (s, 3 H), 2.61 (t) , 2 H), 4.07 (t, 2 H), 6.85 (s, 1 H), 7.21 (d, 2 H), 7.43-7.64 (m, 4 H), 7.66 (d, 2 H), 7.91 (s , 1 H), 8.64 (s, 2 H), 8.21 (s, 1 H), 9.13 (s, 1 H).

實施例72-6：1-[3-(1，1-二氟乙基)-1-(2-甲基苯基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 72-6: 1-[3-(1,1-Difluoroethyl)-1-(2-methylphenyl)-1H-pyrazole-5-yl]-3-(2-{4 -[2-(2-Sideoxy-1-piperidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.34(己烷：乙酸乙酯=1：4)；1H-NMR(DMSO-d6)：δ 1.83-2.04(m，10 H)，2.61(t，2 H)，4.07(t，2 H)，6.65(s，1 H)，7.21(d，2 H)，7.30-7.50(m，4 H)，7.65(d，2 H)，7.91(s，1 H)，8.63(s，2 H)，8.66(s，1 H)，9.11(s，1 H)。 TLC: Rf 0.34 (hexane: ethyl acetate = 1 : 4); 1 H-NMR (DMSO-d 6 ): δ 1.8-2.04 (m, 10 H), 2.61 (t, 2 H), 4.07 (t) , 2 H), 6.65 (s, 1 H), 7.21 (d, 2 H), 7.30-7.50 (m, 4 H), 7.65 (d, 2 H), 7.91 (s, 1 H), 8.63 (s) , 2 H), 8.66 (s, 1 H), 9.11 (s, 1 H).

實施例72-7：1-(3-環丙基-1-苯基-1H-吡唑-5-基)-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 72-7: 1-(3-Cyclopropyl-1-phenyl-1H-pyrazol-5-yl)-3-(2-{4-[2-(2-Sideoxy-1-) Pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.56(二氯甲烷：乙酸乙酯：甲醇=8：4：1)；1H-NMR(DMSO-d6)：δ 0.65-0.75(m，2 H)，0.85-0.95(m，2 H)，1.80-1.95(m，1 H)，2.10-2.25(m，2 H)，2.64(t，2 H)，4.05(t，2 H)，6.16(s，1 H)，7.20(d，2 H)，7.34-7.44(m，1 H)，7.45-7.55(m，4 H)，7.66(d，2 H)，7.89(s，1 H)，8.60-8.70(m，3 H)，9.15(s，1 H)。 TLC: Rf 0.56 (dichloromethane: ethyl acetate:methanol = 8:4:1); 1 H-NMR (DMSO-d 6 ): δ 0.65-0.75 (m, 2 H), 0.85-0.95 (m, 2 H), 1.80-1.95 (m, 1 H), 2.10-2.25 (m, 2 H), 2.64 (t, 2 H), 4.05 (t, 2 H), 6.16 (s, 1 H), 7.20 ( d, 2 H), 7.34-7.44 (m, 1 H), 7.45-7.55 (m, 4 H), 7.66 (d, 2 H), 7.89 (s, 1 H), 8.60-8.70 (m, 3 H ), 9.15 (s, 1 H).

實施例73 Example 73

使用相當之肼衍生物替代(3，4-二甲基苯基)肼鹽酸鹽，使用相當之5-溴噻唑衍生物替代實施例18製造之化合物，進行與實施例62→實施例63→實施例19→實施例20→實施例21相同之操作，獲得具有以下物性值之本發明化合物。 Substituting the equivalent of the indole derivative for the (3,4-dimethylphenyl)phosphonium hydrochloride, using the equivalent 5-bromothiazole derivative in place of the compound produced in Example 18, was carried out with Example 62 → Example 63 → The same procedure as in Example 19 → Example 20 → Example 21 was carried out to obtain a compound of the present invention having the following property values.

實施例73-1：1-[1-(6-甲氧基-3-吡啶基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 73-1:1-[1-(6-Methoxy-3-pyridyl)-3-(2-methyl-2-propyl)-1H-pyrazole-5-yl]-3- (2-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.50(二氯甲烷：乙酸乙酯：甲醇=8：4：1)；1H-NMR(DMSO-d6)：δ 1.26(s，9 H)，2.10-2.23(m，2 H)，2.64(t，2 H)，3.90(s，3 H)，4.05(t，2 H)，6.36(s，1 H)，6.97(d，1 H)，7.21(d，2 H)，7.66(d，2 H)，7.82(dd，1 H)，7.89(s，1 H)，8.29(d，1 H)，8.65(s，3 H)，9.14(s，1 H)。 TLC: Rf 0.50 (dichloromethane: ethyl acetate:methanol = 8:4:1); 1 H-NMR (DMSO-d 6 ): δ 1.26 (s, 9 H), 2.10-2.23 (m, 2 H) ), 2.64(t, 2 H), 3.90 (s, 3 H), 4.05 (t, 2 H), 6.36 (s, 1 H), 6.97 (d, 1 H), 7.21 (d, 2 H), 7.66 (d, 2 H), 7.82 (dd, 1 H), 7.89 (s, 1 H), 8.29 (d, 1 H), 8.65 (s, 3 H), 9.14 (s, 1 H).

實施例73-2：1-[3-(2-甲基-2-丙基)-1-(6-甲基-3-吡啶基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 73-2: 1-[3-(2-Methyl-2-propyl)-1-(6-methyl-3-pyridyl)-1H-pyrazole-5-yl]-3-( 2-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.34(二氯甲烷：乙酸乙酯：甲醇=8：4：1)；1H-NMR(DMSO-d6)：δ 1.27(s，9 H)，2.10-2.23(m，2 H)，2.50(s，3 H)，2.64(t，2 H)，4.05(t，2 H)，6.37(s，1 H)，7.21(d，2 H)，7.40(d，1 H)，7.66(d，2 H)，7.81(dd，1 H)，7.89(s，1 H)，8.58(d，1 H)，8.64(s，2 H)，8.70(s，1 H)，9.18(s，1 H)。 TLC: Rf 0.34 (dichloromethane: ethyl acetate:methanol = 8:4:1); 1 H-NMR (DMSO-d 6 ): δ 1.27 (s, 9 H), 2.10-2.23 (m, 2 H) ), 2.50 (s, 3 H), 2.64 (t, 2 H), 4.05 (t, 2 H), 6.37 (s, 1 H), 7.21 (d, 2 H), 7.40 (d, 1 H), 7.66 (d, 2 H), 7.81 (dd, 1 H), 7.89 (s, 1 H), 8.58 (d, 1 H), 8.64 (s, 2 H), 8.70 (s, 1 H), 9.18 ( s, 1 H).

實施例73-3：1-[3-(2-甲基-2-丙基)-1-(3-吡啶基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 73-3: 1-[3-(2-Methyl-2-propyl)-1-(3-pyridyl)-1H-pyrazole-5-yl]-3-(2-{4- [2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.46(二氯甲烷：乙酸乙酯：甲醇=8：4：1)； 1H-NMR(DMSO-d6)：δ 1.28(s，9 H)，2.10-2.23(m，2 H)，2.64(t，2 H)，4.05(t，2 H)，6.40(s，1 H)，7.21(d，2 H)，7.56(dd，1 H)，7.66(d，2 H)，7.89(s，1 H)，7.92-8.00(m，1 H)，8.57(d，1 H)，8.64(s，2 H)，8.74-8.82(m，2 H)，9.22(s，1 H)。 TLC: Rf 0.46 (dichloromethane: ethyl acetate:methanol = 8:4:1); 1 H-NMR (DMSO-d 6 ): δ 1.28 (s, 9 H), 2.10-2.23 (m, 2 H) ), 2.64 (t, 2 H), 4.05 (t, 2 H), 6.40 (s, 1 H), 7.21 (d, 2 H), 7.56 (dd, 1 H), 7.66 (d, 2 H), 7.89 (s, 1 H), 7.92-8.00 (m, 1 H), 8.57 (d, 1 H), 8.64 (s, 2 H), 8.74-8.82 (m, 2 H), 9.22 (s, 1 H) ).

實施例73-4：1-[1-(6-異丙氧基-3-吡啶基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 73-4: 1-[1-(6-Isopropoxy-3-pyridyl)-3-(2-methyl-2-propyl)-1H-pyrazole-5-yl]-3 -(2-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.40(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 1.32-1.29(m，15 H)，2.16(q，2 H)，2.63(t，2 H)，4.05(t，2 H)，5.26(m，1 H)，6.35(s，1 H)，6.87(d，1 H)，7.20(d，2 H)，7.66(d，2 H)，7.78(dd，1 H)，7.88(s，1 H)，8.25(d，1 H)，8.64(m，3 H)，9.13(s，1 H)。 TLC: Rf 0.40 (ethyl acetate); 1 H-NMR (DMSO -d 6): δ 1.32-1.29 (m, 15 H), 2.16 (q, 2 H), 2.63 (t, 2 H), 4.05 ( t,2 H), 5.26 (m, 1 H), 6.35 (s, 1 H), 6.87 (d, 1 H), 7.20 (d, 2 H), 7.66 (d, 2 H), 7.78 (dd, 1 H), 7.88 (s, 1 H), 8.25 (d, 1 H), 8.64 (m, 3 H), 9.13 (s, 1 H).

實施例73-5：1-[3-(2-甲基-2-丙基)-1-(6-甲基-3-吡啶基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 73-5: 1-[3-(2-Methyl-2-propyl)-1-(6-methyl-3-pyridyl)-1H-pyrazole-5-yl]-3-( 2-{4-[2-(2-Sideoxy-1-piperidyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.63(乙酸乙酯：甲醇=19：1)；1H-NMR(CD3OD)：δ 1.35(s，9 H)，1.86-2.11(m，4 H)，2.60(s，3 H)，2.69(t，2 H)，4.16(t，2 H)，6.42(s，1 H)，7.20(d，2 H)，7.46(d，1 H)，7.65(d，2 H)，7.75(s，1 H)，7.89(dd，1 H)，8.60(d，1 H)，8.62(s，2 H)。 TLC: Rf 0.63 (ethyl acetate:methanol = 19:1); 1 H-NMR (CD 3 OD): δ 1.35 (s, 9 H), 1.86-2.11 (m, 4 H), 2.60 (s, 3) H), 2.69 (t, 2 H), 4.16 (t, 2 H), 6.42 (s, 1 H), 7.20 (d, 2 H), 7.46 (d, 1 H), 7.65 (d, 2 H) , 7.75 (s, 1 H), 7.89 (dd, 1 H), 8.60 (d, 1 H), 8.62 (s, 2 H).

實施例73-6：1-[3-(2-甲基-2-丙基)-1-(3-吡啶基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 73-6: 1-[3-(2-Methyl-2-propyl)-1-(3-pyridyl)-1H-pyrazole-5-yl]-3-(2-{4- [2-(2-Sideoxy-1-piperidyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.21(乙酸乙酯)； 1H-NMR(DMSO-d6)：δ 1.28(s，9 H)，1.83(m，2 H)，1.93(m，2 H)，2.61(t，2 H)，4.07(t，2 H)，6.40(s，1 H)，7.20(dd，2 H)，7.55(dd，1 H)7.64(dd，2 H)，7.90(s，1 H)，7.94(m，1 H)，8.56(dd，1 H)，8.64(s，2 H)，8.75(d，1 H)，8.78(s，1 H)，9.21(s，1 H)。 TLC: Rf 0.21 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 1.28 (s, 9 H), 1.83 (m, 2 H), 1.93 (m, 2 H), 2.61 (t, 2 H), 4.07 (t, 2 H), 6.40 (s, 1 H), 7.20 (dd, 2 H), 7.55 (dd, 1 H) 7.64 (dd, 2 H), 7.90 (s, 1 H) , 7.94 (m, 1 H), 8.56 (dd, 1 H), 8.64 (s, 2 H), 8.75 (d, 1 H), 8.78 (s, 1 H), 9.21. (s, 1 H).

實施例74：1-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-(4-吡啶基)-5-(三氟甲基)苯基]脲 Example 74: 1-(2-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)- 3-[2-(4-pyridyl)-5-(trifluoromethyl)phenyl]urea

使用2-(吡啶-4-基)-5-(三氟甲基)苯胺替代實施例7製造之化合物，使用1-(5-溴噻唑-2-基)吡咯啶-2-酮替代實施例18製造之化合物，進行與實施例8→實施例19→實施例20→實施例21相同之操作，獲得具有以下物性值之本發明化合物。 Substituting 2-(pyridin-4-yl)-5-(trifluoromethyl)aniline for the compound produced in Example 7, using 1-(5-bromothiazol-2-yl)pyrrolidin-2-one instead of the example The compound produced in the same manner as in Example 8 → Example 19 → Example 20 → Example 21 was obtained to obtain a compound of the present invention having the following properties.

TLC：Rf 0.27(二氯甲烷：乙酸乙酯：甲醇=8：4：1)；1H-NMR(DMSO-d6)：δ 2.10-2.23(m，2 H)，2.64(t，2 H)，4.05(t，2 H)，7.21(d，2 H)，7.46-7.56(m，4 H)，7.67(d，2 H)，7.89(s，1 H)，8.23(s，1 H)，8.38(s，1H)，8.64(s，2 H)，8.72(d，2 H)，9.25(s，1 H)。 TLC: Rf 0.27 (dichloromethane: ethyl acetate:methanol = 8:4:1); 1 H-NMR (DMSO-d 6 ): δ 2.10-2.23 (m, 2 H), 2.64 (t, 2 H) ), 4.05 (t, 2 H), 7.21 (d, 2 H), 7.46-7.56 (m, 4 H), 7.67 (d, 2 H), 7.89 (s, 1 H), 8.23 (s, 1 H) ), 8.38 (s, 1H), 8.64 (s, 2 H), 8.72 (d, 2 H), 9.25 (s, 1 H).

實施例75：1-(2-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-(6-甲基-3-吡啶基)-5-(三氟甲基)苯基]脲 Example 75: 1-(2-{4-[2-(ethylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-[2-(6- Methyl-3-pyridyl)-5-(trifluoromethyl)phenyl]urea

使用2-溴-5-(三氟甲基)苯胺替代2-氯-3-硝基-5-(三氟甲基)吡啶，使用6-甲基吡啶-3-硼酸替代(6-(三氟甲基)吡啶-3-基)硼酸，使用第三丁基(5-溴噻唑-2-基)(乙基)胺基甲酸酯替代實施例18製造之化合物，進行與實施例6→實施例5→實施例8→實施例19→實施例20→實施例21相同之操作，獲得具有以下物性值之本發明化合物。 Replace 2-chloro-3-nitro-5-(trifluoromethyl)pyridine with 2-bromo-5-(trifluoromethyl)aniline and replace with 6-methylpyridine-3-boronic acid (6-(three) Fluoromethyl)pyridin-3-yl)boronic acid, using a third butyl (5-bromothiazol-2-yl)(ethyl) urethane instead of the compound produced in Example 18, was carried out with Example 6 → The same procedure as in Example 5 → Example 8 → Example 19 → Example 20 → Example 21 was carried out to obtain a compound of the present invention having the following physical properties.

TLC：Rf 0.66(乙酸乙酯：甲醇=19：1)；1H-NMR(DMSO-d6)：δ 1.16(t，3 H)，2.55(s，3 H)，3.25(m，2 H)，7.12(d，2 H)，7.40-7.50(m，6 H)，7.71-7.77(m，2 H)，8.17(s，1 H)，8.40(s，1 H)，8.49(s，1 H)，8.63(s，2 H)，9.24(s，1 H)。 TLC: Rf 0.66 (ethyl acetate:methanol = 19:1); 1 H-NMR (DMSO-d 6 ): δ 1.16 (t, 3 H), 2.55 (s, 3 H), 3.25 (m, 2 H) ), 7.12 (d, 2 H), 7.40-7.50 (m, 6 H), 7.71-7.77 (m, 2 H), 8.17 (s, 1 H), 8.40 (s, 1 H), 8.49 (s, 1 H), 8.63 (s, 2 H), 9.24 (s, 1 H).

實施例76：1-[2-(3，4-二甲基苯基)-5-甲基-3-吡啶基]-3-(2-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 76: 1-[2-(3,4-Dimethylphenyl)-5-methyl-3-pyridyl]-3-(2-{4-[2-(ethylamino)-1 , 3-thiazole-5-yl]phenoxy}-5-pyrimidinyl)urea

使用2-溴-5-甲基-3-硝基吡啶替代2-氯-3-硝基-5-(三氟甲基)吡啶，使用3，4-二甲基苯基硼酸替代(6-(三氟甲基)吡啶-3-基)硼酸，使用第三丁基(5-溴噻唑-2-基)(乙基)胺基甲酸酯替代實施例18製造之化合物，進行與實施例6→實施例5→實施例8→實施例19→實施例20→實施例21相同之操作，獲得具有以下物性值之本發明化合物。 Substituting 2-bromo-5-methyl-3-nitropyridine for 2-chloro-3-nitro-5-(trifluoromethyl)pyridine and replacing with 3,4-dimethylphenylboronic acid (6- (Trifluoromethyl)pyridin-3-yl)boronic acid, using a third butyl (5-bromothiazol-2-yl)(ethyl) urethane instead of the compound produced in Example 18, and the examples 6→Example 5→Example 8→Example 19→Example 20→Example 21 The same procedure as in Example 21 was carried out to obtain a compound of the present invention having the following physical properties.

TLC：Rf 0.52(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 1.16(t，3 H)，2.24(s，6 H)，2.32(s，3 H)，3.26(m，2 H)，7.12(d，2 H)，7.25(s，2 H)，7.33(s，1 H)，7.42(s，1 H)，7.43(d，2 H)，7.71(t，1 H)，8.01(s，1 H)，8.13(s，1 H)， 8.17(s，1 H)，8.64(s，2 H)，9.30(s，1 H)。 TLC: Rf 0.52 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 1.16 (t, 3 H), 2.24 (s, 6 H), 2.32 (s, 3 H), 3.26 (m, 2 H), 7.12 (d, 2 H), 7.25 (s, 2 H), 7.33 (s, 1 H), 7.42 (s, 1 H), 7.43 (d, 2 H), 7.71 (t, 1 H) ), 8.01 (s, 1 H), 8.13 (s, 1 H), 8.17 (s, 1 H), 8.64 (s, 2 H), 9.30 (s, 1 H).

實施例77：1-[2-(3，4-二甲基苯基)-3-吡啶基]-3-(2-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 77: 1-[2-(3,4-Dimethylphenyl)-3-pyridyl]-3-(2-{4-[2-(ethylamino)-1,3-thiazole- 5-yl]phenoxy}-5-pyrimidinyl)urea

使用2-溴-3-硝基吡啶替代2-氯-3-硝基-5-(三氟甲基)吡啶，使用3，4-二甲基苯基硼酸替代(6-(三氟甲基)吡啶-3-基)硼酸，使用第三丁基(5-溴噻唑-2-基)(乙基)胺基甲酸酯替代實施例18製造之化合物，進行與實施例6→實施例5→實施例8→實施例19→實施例20→實施例21相同之操作，獲得具有以下物性值之本發明化 Substituting 2-bromo-3-nitropyridine for 2-chloro-3-nitro-5-(trifluoromethyl)pyridine and replacing with 3,4-dimethylphenylboronic acid (6-(trifluoromethyl) Pyridin-3-yl)boronic acid, using a third butyl (5-bromothiazol-2-yl)(ethyl) urethane instead of the compound produced in Example 18, and Example 6 → Example 5 → Example 8 → Example 19 → Example 20 → Example 21 The same operation was carried out to obtain the present invention having the following physical property values.

TLC：Rf 0.55(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 1.16(t，3 H)，2.29(s，6 H)，3.24-3.32(m，2 H)，7.12(d，2 H)，7.27-7.34(m，4 H)，7.42(s，1 H)，7.44(d，2 H)，7.71(t，1 H)，8.06(s，1 H)，8.27(dd，1 H)，8.33(dd，1 H)，8.64(s，2 H)，9.31(s，1 H)。 TLC: Rf 0.55 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 1.16 (t, 3 H), 2.29 (s, 6 H), 3.24 - 3.32 (m, 2 H), 7.12 ( d, 2 H), 7.27-7.34 (m, 4 H), 7.42 (s, 1 H), 7.44 (d, 2 H), 7.71 (t, 1 H), 8.06 (s, 1 H), 8.27 ( Dd, 1 H), 8.33 (dd, 1 H), 8.64 (s, 2 H), 9.31 (s, 1 H).

實施例78：1-[2-(4-嗎啉基)-5-(三氟甲基)苯基]-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 78: 1-[2-(4-Morpholinyl)-5-(trifluoromethyl)phenyl]-3-(2-{4-[2-(2- oxo-l-per Pyridyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

使用3-胺基-4-(4-嗎啉基)三氟甲苯替代實施例7製造之化合物，進行與實施例8→實施例9相同之操作，獲得具有以下物性值之本發明化合物。 The compound produced in Example 7 was replaced with 3-amino-4-(4-morpholinyl)benzotrifluoride, and the same procedure as in Example 8 - Example 9 was carried out to obtain a compound of the present invention having the following properties.

TLC：Rf 0.31(己烷：乙酸乙酯=1：4)；1H-NMR(DMSO-d6)：δ 1.75-2.00(m，4 H)，2.61(t，2 H)，3.80-3.90 (m，4 H)，4.80-4.90(m，4 H)，4.07(t，2 H)，7.23(d，2 H)，7.24-7.36(m，2 H)，7.66(d，2 H)，7.91(s，1 H)，8.34(s，1 H)，8.42(s，1 H)，8.73(s，2 H)，9.86(s，1 H)。 TLC: Rf 0.31 (hexane: ethyl acetate = 1 : 4); 1 H-NMR (DMSO-d 6 ): δ 1.75 - 2.00 (m, 4 H), 2.61 (t, 2 H), 3.80 - 3.90 (m, 4 H), 4.80-4.90 (m, 4 H), 4.07 (t, 2 H), 7.23 (d, 2 H), 7.24-7.36 (m, 2 H), 7.66 (d, 2 H) , 7.91 (s, 1 H), 8.34 (s, 1 H), 8.42 (s, 1 H), 8.73 (s, 2 H), 9.86 (s, 1 H).

實施例79：1-[2-(4-甲基-1-哌基)-5-(三氟甲基)苯基]-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 79: 1-[2-(4-methyl-1-piperidyl) 5-(3-trifluoromethyl)phenyl]-3-(2-{4-[2-(2-o-oxy-1-piperidyl)-1,3-thiazol-5-yl] Phenoxy}-5-pyrimidinyl)urea

使用2-(4-甲基哌-1-基)-5-(三氟甲基)苯胺替代實施例7製造之化合物，進行與實施例8→實施例9相同之操作，獲得具有以下物性值之本發明化合物。 Using 2-(4-methylperazine In the same manner as in Example 8 → Example 9, the compound of the present invention was subjected to the same procedure as in Example 8 to Example 9, to obtain a compound of the present invention having the following properties.

TLC：Rf 0.68(乙酸乙酯：甲醇：氨水=9：1：0.5)；1H-NMR(DMSO-d6)：δ 1.80-1.99(m，4 H)，2.28(s，3 H)，2.55-2.70(m，6 H)，3.80-3.90(m，4 H)，4.07(t，2 H)，7.23(d，2 H)，7.30-7.40(m，2 H)，7.66(d，2 H)，7.91(s，1 H)，8.24(s，1 H)，8.34(s，1 H)，8.73(s，2 H)，9.89(s，1 H)。 TLC: Rf 0.68 (ethyl acetate:methanol:methanol = 9:1: 0.5); 1 H-NMR (DMSO-d 6 ): δ 1.80-1.99 (m, 4 H), 2.28 (s, 3 H), 2.55-2.70 (m, 6 H), 3.80-3.90 (m, 4 H), 4.07 (t, 2 H), 7.23 (d, 2 H), 7.30-7.40 (m, 2 H), 7.66 (d, 2 H), 7.91 (s, 1 H), 8.24 (s, 1 H), 8.34 (s, 1 H), 8.73 (s, 2 H), 9.89 (s, 1 H).

實施例80 Example 80

使用相當之肼衍生物替代(3，4-二甲基苯基)肼鹽酸鹽，使用1-(5-溴噻唑-2-基)吡咯啶-2-酮替代實施例18製造之化合物，進行與實施例62→實施例63→實施例19→實施例20→實施例21相同之操作，獲得具有以下物性值之本發明化合物。 Substituting the equivalent hydrazine derivative for (3,4-dimethylphenyl)phosphonium hydrochloride, using 1-(5-bromothiazol-2-yl)pyrrolidin-2-one in place of the compound produced in Example 18, The same procedure as in Example 62 → Example 63 → Example 19 → Example 20 → Example 21 was carried out to obtain a compound of the present invention having the following property values.

實施例80-1：1-[3-(2-甲基-2-丙基)-1-(1，2，3，4-四氫-2-萘基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 80-1:1-[3-(2-Methyl-2-propyl)-1-(1,2,3,4-tetrahydro-2-naphthalenyl)-1H-pyrazole-5- 3-(2-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

[化69] [化69]

TLC：Rf 0.64(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 1.22(s，9 H)，2.00-2.25(m，4 H)，2.64(t，2 H)，2.88-3.04(m，3 H)，3.16-3.22(m，1 H)，4.05(t，2 H)，4.38(m，1 H)，6.08(s，1 H)，7.08-7.13(m，4 H)，7.21(d，2 H)，7.67(d，2 H)，7.89(s，1 H)，8.68(s，2 H)，8.71(s，1 H)，9.01(s，1 H)。 TLC: Rf 0.64 (ethyl acetate); 1 H-NMR (DMSO -d 6): δ 1.22 (s, 9 H), 2.00-2.25 (m, 4 H), 2.64 (t, 2 H), 2.88- 3.04 (m, 3 H), 3.16-3.22 (m, 1 H), 4.05 (t, 2 H), 4.38 (m, 1 H), 6.08 (s, 1 H), 7.08-7.13 (m, 4 H) ), 7.21 (d, 2 H), 7.67 (d, 2 H), 7.89 (s, 1 H), 8.68 (s, 2 H), 8.71 (s, 1 H), 9.01 (s, 1 H).

實施例80-2：1-[3-(2-甲基-2-丙基)-1-(四氫-2H-吡喃-4-基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 80-2: 1-[3-(2-Methyl-2-propyl)-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-5-yl]-3 -(2-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.34(乙酸乙酯：甲醇=9：1)；1H-NMR(DMSO-d6)：δ 1.21(s，9 H)，1.76(m，2 H)，2.01(m，2 H)，2.16(m，2 H)，2.64(t，2 H)，3.40(m，2 H)，3.95(m，2 H)，4.05(t，2 H)，4.20(m，1 H)，6.03(s，1 H)，7.22(d，2 H)，7.68(d，2 H)，7.89(s，1 H)，8.65(s，1 H)，8.70(s，2 H)，9.06(s，1 H)。 TLC: Rf 0.34 (ethyl acetate:methanol = 9:1); 1 H-NMR (DMSO-d 6 ): δ 1.21. (s, 9 H), 1.76 (m, 2 H), 2.01 (m, 2 H) ), 2.16 (m, 2 H), 2.64 (t, 2 H), 3.40 (m, 2 H), 3.95 (m, 2 H), 4.05 (t, 2 H), 4.20 (m, 1 H), 6.03 (s, 1 H), 7.22 (d, 2 H), 7.68 (d, 2 H), 7.89 (s, 1 H), 8.65 (s, 1 H), 8.70 (s, 2 H), 9.06 ( s, 1 H).

實施例80-3：1-[1-環己基-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 80-3: 1-[1-Cyclohexyl-3-(2-methyl-2-propyl)-1H-pyrazol-5-yl]-3-(2-{4-[2-( 2-sided oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.63(二氯甲烷：乙酸乙酯：甲醇=8：4：1)；1H-NMR(DMSO-d6)：δ 1.20(s，9 H)，1.15-1.40(m，4 H)，1.57-1.88(m，6 H)，2.10-2.23(m，2 H)，2.64(t，2 H)，3.86-4.00(m，1 H)，4.05(t，2 H)，6.01(s，1 H)，7.22(d，2 H)，7.67(d，2 H)，7.90(s，1 H)，8.60(s，1 H)，8.71(s，2 H)，9.03(s，1 H)。 TLC: Rf 0.63 (dichloromethane: ethyl acetate:methanol = 8:4:1); 1 H-NMR (DMSO-d 6 ): δ 1.20 (s, 9 H), 1.15-1.40 (m, 4 H) ), 1.57-1.88 (m, 6 H), 2.10-2.23 (m, 2 H), 2.64 (t, 2 H), 3.86-4.00 (m, 1 H), 4.05 (t, 2 H), 6.01 ( s, 1 H), 7.22 (d, 2 H), 7.67 (d, 2 H), 7.90 (s, 1 H), 8.60 (s, 1 H), 8.71 (s, 2 H), 9.03 (s, 1 H).

實施例81：1-(2-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-(3-吡啶基)-5-(三氟甲基)苯基]脲 Example 81:1-(2-{4-[2-(ethylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-[2-(3- Pyridyl)-5-(trifluoromethyl)phenyl]urea

使用2-(吡啶-2-基)-5-(三氟甲基)苯胺替代實施例7製造之化合物，使用第三丁基(5-溴噻唑-2-基)(乙基)胺基甲酸酯替代實施例18製造之化合物，進行與實施例8→實施例19→實施例20→實施例21相同之操作，獲得具有以下物性值之本發明化合物。 Substituting 2-(pyridin-2-yl)-5-(trifluoromethyl)aniline for the compound produced in Example 7, using a third butyl (5-bromothiazol-2-yl)(ethyl)amino group The acid ester was replaced by the compound produced in Example 18, and the same procedure as in Example 8 → Example 19 → Example 20 → Example 21 was carried out to obtain a compound of the present invention having the following property values.

TLC：Rf 0.54(乙酸乙酯：己烷=9：1)；1H-NMR(DMSO-d6)：δ 1.16(t，3 H)，3.26(m，2 H)，7.13(d，2 H)，7.42-7.58(m，6 H)，7.72(t，1 H)，7.89(dt，1 H)，8.23(s，1 H)，8.38(s，1 H)，8.62(s，2 H)，8.65(dd，1 H)，8.68(dd，1 H)，9.22(s，1 H)。 TLC: Rf 0.54 (ethyl acetate: hexane = 9: 1); 1 H -NMR (DMSO-d 6): δ 1.16 (t, 3 H), 3.26 (m, 2 H), 7.13 (d, 2 H), 7.42-7.58 (m, 6 H), 7.72 (t, 1 H), 7.89 (dt, 1 H), 8.23 (s, 1 H), 8.38 (s, 1 H), 8.62 (s, 2) H), 8.65 (dd, 1 H), 8.68 (dd, 1 H), 9.22 (s, 1 H).

實施例82：1-[2-環己基-5-(三氟甲基)-3-吡啶基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 82: 1-[2-Cyclohexyl-5-(trifluoromethyl)-3-pyridyl]-3-(2-{4-[2-(2-o-oxy-1-pyrrolidinyl) )-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

使用2-環己基-5-(三氟甲基)-吡啶-3-胺替代實施例7製造之化合物，使用1-(5-溴噻唑-2-基)吡咯啶-2-酮替代實施例18製造之化合物，進行與實施例8→實施例19→實施例20→實施例21相同之操作，獲得具有以下物性值之本發明化合物。 Substituting 2-cyclohexyl-5-(trifluoromethyl)-pyridin-3-amine for the compound produced in Example 7, using 1-(5-bromothiazol-2-yl)pyrrolidin-2-one instead of the example The compound produced in the same manner as in Example 8 → Example 19 → Example 20 → Example 21 was obtained to obtain a compound of the present invention having the following properties.

TLC：Rf 0.60(二氯甲烷：乙酸乙酯：甲醇=8：4：1)；1H-NMR(DMSO-d6)：δ 1.20-1.70(m，6 H)，1.70-1.90(m，4 H)，2.10-2.23(m，2 H)，2.64(t，2 H)，2.95-3.07(m，1 H)，4.05(t，2 H)，7.23(d，2 H)，7.68(d，2 H)，7.90(s，1 H)，8.51(s，1 H)，8.61(s，2 H)，8.75(s，2 H)，9.33(s，1 H)。 TLC: Rf 0.60 (dichloromethane: ethyl acetate:methanol = 8:4:1); 1 H-NMR (DMSO-d 6 ): δ 1.20-1.70 (m, 6 H), 1.70-1.90 (m, 4 H), 2.10-2.23 (m, 2 H), 2.64 (t, 2 H), 2.95-3.07 (m, 1 H), 4.05 (t, 2 H), 7.23 (d, 2 H), 7.68 ( d, 2 H), 7.90 (s, 1 H), 8.51 (s, 1 H), 8.61 (s, 2 H), 8.75 (s, 2 H), 9.33 (s, 1 H).

實施例83：1-[2-(3，4-二甲基苯基)-5-甲基-3-吡啶基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 83: 1-[2-(3,4-Dimethylphenyl)-5-methyl-3-pyridyl]-3-(2-{4-[2-(2-Sideoxy)- 1-pyrrolidyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

使用2-溴-5-甲基-3-硝基吡啶替代2-氯-3-硝基-5-(三氟甲基)吡啶，使用3，4-二甲基苯基硼酸替代(6-(三氟甲基)吡啶-3-基)硼酸，使用1-(5-溴噻唑-2-基)吡咯啶-2-酮替代實施例18製造之化合物，進行與實施例6→實施例5→實施例8→實施例19→實施例20→實施例21相同之操作，獲得具有以下物性值之本發明化合物。 Substituting 2-bromo-5-methyl-3-nitropyridine for 2-chloro-3-nitro-5-(trifluoromethyl)pyridine and replacing with 3,4-dimethylphenylboronic acid (6- (Trifluoromethyl)pyridin-3-yl)boronic acid, using 1-(5-bromothiazol-2-yl)pyrrolidin-2-one in place of the compound produced in Example 18, and Example 6→Example 5 → Example 8 → Example 19 → Example 20 → Example 21 The same procedure as in Example 21 was carried out to obtain a compound of the present invention having the following physical properties.

TLC：Rf 0.53(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 2.14(m，2 H)，2.28(s，3 H)，2.32(s，6 H)，2.64(t，2 H)，4.05(t，2 H)，7.20-7.33(m，5 H)，7.65(dd，2 H)，7.89(d，1 H)，8.02(s，1 H)，8.13(s，1 H)，8.18(s，1 H)，8.66(s，2 H)，9.32(s，1 H)。 TLC: Rf 0.53 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 2.14 (m, 2 H), 2.28 (s, 3 H), 2.32 (s, 6 H), 2.64 (t, 2 H), 4.05 (t, 2 H), 7.20-7.33 (m, 5 H), 7.65 (dd, 2 H), 7.89 (d, 1 H), 8.02 (s, 1 H), 8.13 (s, 1 H), 8.18 (s, 1 H), 8.66 (s, 2 H), 9.32 (s, 1 H).

實施例84 Example 84

使用相當之胺衍生物替代實施例7製造之化合物，使用相當之5-溴噻唑衍生物替代實施例18製造之化合物，使用2-氯-5-硝基嘧啶、或替代2-氯-5-硝基嘧啶之2-氯-5-硝基吡啶，使用4-溴苯酚、或替代4-溴苯酚之6-溴吡啶-3-醇，進行與實施例8→實施例12→實施例13→實施例19→實施例20→實施例21相同之操作，獲得具有以下物性值之本發明化合物。 Substituting a comparable amine derivative for the compound produced in Example 7, using a comparable 5-bromothiazole derivative in place of the compound produced in Example 18, using 2-chloro-5-nitropyrimidine, or replacing 2-chloro-5- 2-Chloro-5-nitropyridine of nitropyrimidine, using 4-bromophenol or 6-bromopyridin-3-ol instead of 4-bromophenol, and Example 8→Example 12→Example 13→ The same procedure as in Example 19 → Example 20 → Example 21 was carried out to obtain a compound of the present invention having the following property values.

實施例84-1：1-[2-(3，4-二甲基苯基)-3-吡啶基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 84-1:1-[2-(3,4-Dimethylphenyl)-3-pyridyl]-3-(2-{4-[2-(2-Sideoxy-1-pyrrole) Pyridyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.69(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 2.12(m，2 H)，2.28(s，6 H)，2.60(t，2 H)，4.03(t，2 H)，7.17(d，2 H)，7.23-7.32(m，4 H)，7.62(d，2 H)，7.85(d，1 H)，8.03(s，1 H)，8.24(d，1 H)，8.29(d，1 H)，8.62(s，2 H)，9.29(s，1 H)。 TLC: Rf 0.69 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 2.12 (m, 2 H), 2.28 (s, 6 H), 2.60 (t, 2 H), 4.03 (t, 2 H), 7.17 (d, 2 H), 7.23-7.32 (m, 4 H), 7.62 (d, 2 H), 7.85 (d, 1 H), 8.03 (s, 1 H), 8.24 (d, 1 H), 8.29 (d, 1 H), 8.62 (s, 2 H), 9.29 (s, 1 H).

實施例84-2：1-(3-異丙基-1-苯基-1H-吡唑-5-基)-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 84-2: 1-(3-Isopropyl-1-phenyl-1H-pyrazol-5-yl)-3-(2-{4-[2-(2-Sideoxy-1-) Pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.55(二氯甲烷：乙酸乙酯：甲醇=8：4：1)；1H-NMR(DMSO-d6)：δ 1.22(d，6 H)，2.10-2.23(m，2 H)，2.64(t，2 H)，2.80-2.95(m，1 H)，4.05(t，2 H)，6.31(s，1 H)，7.20(d，2 H)，7.34-7.44(m，1 H)，7.46-7.54(m，4 H)，7.66(d，2 H)，7.88(s，1 H)，8.62-8.68(m，3 H)，9.17(s，1 H)。 TLC: Rf 0.55 (dichloromethane: ethyl acetate:methanol = 8:4:1); 1 H-NMR (DMSO-d 6 ): δ 1.22 (d, 6 H), 2.10-2.23 (m, 2 H) ), 2.64 (t, 2 H), 2.80-2.95 (m, 1 H), 4.05 (t, 2 H), 6.31 (s, 1 H), 7.20 (d, 2 H), 7.34-7.44 (m, 1 H), 7.46-7.54 (m, 4 H), 7.66 (d, 2 H), 7.88 (s, 1 H), 8.62-8.68 (m, 3 H), 9.17 (s, 1 H).

實施例84-3：1-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-(3-吡啶基)-5-(三氟甲基)苯基]脲 Example 84-3: 1-(2-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl )-3-[2-(3-pyridyl)-5-(trifluoromethyl)phenyl]urea

TLC：Rf 0.26(乙酸乙酯：甲醇=19：1)；1H-NMR(DMSO-d6)：δ 2.16(q，2 H)，2.61(t，2 H)，4.05(t，2 H)，7.21(d，2 H)，7.46-7.57(m，3 H)，7.66(d，2 H)，7.82-7.92(m，2 H)，8.23(s，1 H)，8.38(s，1 H)，8.63-8.68(m，4 H)，9.23(s，1 H)。 TLC: Rf 0.26 (ethyl acetate:methanol = 19:1); 1 H-NMR (DMSO-d 6 ): δ 2.16 (q, 2 H), 2.61 (t, 2 H), 4.05 (t, 2 H) ), 7.21 (d, 2 H), 7.46-7.57 (m, 3 H), 7.66 (d, 2 H), 7.82-7.92 (m, 2 H), 8.23 (s, 1 H), 8.38 (s, 1 H), 8.63 - 8.68 (m, 4 H), 9.23 (s, 1 H).

實施例84-4：1-(6-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)-3-[2-(4-吡啶基)-5-(三氟甲基)苯基]脲 Example 84-4: 1-(6-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-3-pyridyl )-3-[2-(4-pyridyl)-5-(trifluoromethyl)phenyl]urea

TLC：Rf 0.17(乙酸乙酯：甲醇=19：1)；1H-NMR(DMSO-d6)：δ 2.16(q，2 H)，2.64(t，2 H)，4.04(t，2 H)，7.02(d，1 H)，7.11(d，2 H)，7.46-7.54(m，4 H)，7.64(d，2 H)，7.86(s，1 H)，7.98(dd，1 H)，8.09-8.10(m，2 H)，8.42(s，1 H)，8.72(d，2 H)，9.19(s，1 H)。 TLC: Rf 0.17 (ethyl acetate: methanol = 19: 1); 1 H -NMR (DMSO-d 6): δ 2.16 (q, 2 H), 2.64 (t, 2 H), 4.04 (t, 2 H ), 7.02 (d, 1 H), 7.11 (d, 2 H), 7.46-7.54 (m, 4 H), 7.64 (d, 2 H), 7.86 (s, 1 H), 7.98 (dd, 1 H) ), 8.09-8.10 (m, 2 H), 8.42 (s, 1 H), 8.72 (d, 2 H), 9.19 (s, 1 H).

實施例84-5：1-[6’-甲基-5-(三氟甲基)-2，3’-二吡啶-3-基]-3-(6-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-3- 吡啶基)脲 Example 84-5: 1-[6'-Methyl-5-(trifluoromethyl)-2,3'-dipyridin-3-yl]-3-(6-{4-[2-(2) -Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-3- Pyridyl)urea

TLC：Rf 0.35(乙酸乙酯：甲醇=19：1)；1H-NMR(DMSO-d6)：δ 2.16(q，2 H)，2.60(s，3 H)，2.63(t，2 H)，4.04(t，2 H)，7.04(d，1 H)，7.12(d，2 H)，7.45(d，1 H)，7.64(d，2 H)，7.89(s，1 H)，7.96(dd，1 H)，8.01(dd，1 H)，8.12(d，1 H)，8.42(d，1 H)，8.68-8.76(m，2 H)，8.78(s，1 H)，9.30(s，1 H)。 TLC: Rf 0.35 (ethyl acetate:methanol = 19:1); 1 H-NMR (DMSO-d 6 ): δ 2.16 (q, 2 H), 2.60 (s, 3 H), 2.63 (t, 2 H) ), 4.04 (t, 2 H), 7.04 (d, 1 H), 7.12 (d, 2 H), 7.45 (d, 1 H), 7.64 (d, 2 H), 7.89 (s, 1 H), 7.96 (dd, 1 H), 8.01 (dd, 1 H), 8.12 (d, 1 H), 8.42 (d, 1 H), 8.68-8.76 (m, 2 H), 8.78 (s, 1 H), 9.30 (s, 1 H).

實施例84-6：1-(6-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)-3-[2-(3-吡啶基)-5-(三氟甲基)苯基]脲 Example 84-6: 1-(6-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-3-pyridyl )-3-[2-(3-pyridyl)-5-(trifluoromethyl)phenyl]urea

TLC：Rf 0.23(乙酸乙酯：甲醇=19：1)；1H-NMR(DMSO-d6)：δ 2.16(q，2 H)，2.64(t，2 H)，4.04(t，2 H)，7.02(d，1 H)，7.11(d，2 H)，7.44-7.52(m，2 H)，7.56(dd，1 H)，7.64(d，2 H)，7.86-7.91(2 H)，7.98(dd，1 H)，8.08-8.09(m，2 H)，8.42(s，1 H)，8.65(d，1 H)，8.68(dd，1 H)，9.17(s，1 H)。 TLC: Rf 0.23 (ethyl acetate:methanol = 19:1); 1 H-NMR (DMSO-d 6 ): δ 2.16 (q, 2 H), 2.64 (t, 2 H), 4.04 (t, 2 H) ), 7.02 (d, 1 H), 7.11 (d, 2 H), 7.44 - 7.52 (m, 2 H), 7.56 (dd, 1 H), 7.64 (d, 2 H), 7.86-7.91 (2 H ), 7.98 (dd, 1 H), 8.08-8.09 (m, 2 H), 8.42 (s, 1 H), 8.65 (d, 1 H), 8.68 (dd, 1 H), 9.17 (s, 1 H) ).

實施例84-7：1-(6-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)-3-[2-苯基-5-(三氟甲基)-3-吡啶基]脲 Example 84-7: 1-(6-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-3-pyridyl )-3-[2-phenyl-5-(trifluoromethyl)-3-pyridyl]urea

TLC：Rf 0.58(乙酸乙酯：甲醇=19：1)；1H-NMR(DMSO-d6)：δ 2.16(q，2 H)，2.64(t，2 H)，4.04(s，2 H)，7.04(d，1 H)，7.12(d，2 H)，7.55-7.67(m，7 H)，7.87(s，1 H)，8.01(dd，1 H)，8.12(d，1 H)，8.29(s，1 H)，8.70(s，1 H)，8.79(s，1 H)，9.40(s，1 H)。 TLC: Rf 0.58 (ethyl acetate:methanol = 19:1); 1 H-NMR (DMSO-d 6 ): δ 2.16 (q, 2 H), 2.64 (t, 2 H), 4.04 (s, 2 H) ), 7.04 (d, 1 H), 7.12 (d, 2 H), 7.55-7.67 (m, 7 H), 7.87 (s, 1 H), 8.01 (dd, 1 H), 8.12 (d, 1 H) ), 8.29 (s, 1 H), 8.70 (s, 1 H), 8.79 (s, 1 H), 9.40 (s, 1 H).

實施例84-8：1-(6-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)-3-[5-(三氟甲基)-2，4’-二吡啶-3-基]脲 Example 84-8: 1-(6-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-3-pyridyl )-3-[5-(trifluoromethyl)-2,4'-dipyridin-3-yl]urea

TLC：Rf 0.11(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 2.16(t，2 H)，2.64(t，2 H)，4.04(t，2 H)，7.04(d，1 H)，7.12(d，2 H)，7.63-7.68(m，4 H)，7.87(s，1 H)，8.00(dd，1 H)，8.11(d，1 H)，8.42(s，1 H)，8.76(m，4 H)，9.30(s，1 H)。 TLC: Rf 0.11 (ethyl acetate); 1 H-NMR (DMSO -d 6): δ 2.16 (t, 2 H), 2.64 (t, 2 H), 4.04 (t, 2 H), 7.04 (d, 1 H), 7.12 (d, 2 H), 7.63-7.68 (m, 4 H), 7.87 (s, 1 H), 8.00 (dd, 1 H), 8.11 (d, 1 H), 8.42 (s, 1 H), 8.76 (m, 4 H), 9.30 (s, 1 H).

實施例84-9：1-[2-(4-甲基苯基)-5-(三氟甲基)-3-吡啶基]-3-(6-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)脲 Example 84-9: 1-[2-(4-Methylphenyl)-5-(trifluoromethyl)-3-pyridyl]-3-(6-{4-[2-(2- side) Oxy-1-pyrrolidyl)-1,3-thiazol-5-yl]phenoxy}-3-pyridyl)urea

TLC：Rf 0.72(乙酸乙酯：甲醇=19：1)；1H-NMR(DMSO-d6)：δ 2.16(q，2 H)，2.40(s，3 H)，2.64(t，2 H)，4.03(t，2 H)，7.04(d，1 H)，7.12(d，2 H)，7.38(d，2 H)，7.54(d，2 H)，7.64(d，2 H)，7.89(s，1 H)，8.02(dd，1 H)，8.11(d，1 H)，8.26(s，1 H)，8.67(s，1 H)，8.79(s，1 H)，9.42(s，1 H)。 TLC: Rf 0.72 (ethyl acetate: methanol = 19: 1); 1 H -NMR (DMSO-d 6): δ 2.16 (q, 2 H), 2.40 (s, 3 H), 2.64 (t, 2 H ), 4.03 (t, 2 H), 7.04 (d, 1 H), 7.12 (d, 2 H), 7.38 (d, 2 H), 7.54 (d, 2 H), 7.64 (d, 2 H), 7.89 (s, 1 H), 8.02 (dd, 1 H), 8.11 (d, 1 H), 8.26 (s, 1 H), 8.67 (s, 1 H), 8.79 (s, 1 H), 9.42 ( s, 1 H).

實施例84-10：1-[2-(6-甲基-3-吡啶基)-5-(三氟甲基)苯基]-3-(6-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)脲 Example 84-10: 1-[2-(6-Methyl-3-pyridyl)-5-(trifluoromethyl)phenyl]-3-(6-{4-[2-(2- side) Oxy-1-pyrrolidyl)-1,3-thiazol-5-yl]phenoxy}-3-pyridyl)urea

TLC：Rf 0.28(乙酸乙酯：甲醇=19：1)；1H-NMR(DMSO-d6)：δ 2.16(q，2 H)，2.55(s，3 H)，2.64(t，2 H)，4.04(t，2 H)，7.02(d，1 H)，7.11(d，2 H)，7.41-7.48(m，3 H)，7.64(d，2 H)，7.77(dd，1 H)，7.86(s，1 H)，8.11(dd，1 H)，8.06(s，1 H)，8.09(d，1 H)，8.44(s，1 H)，8.50(d，1 H)，9.21(s，1 H)。 TLC: Rf 0.28 (ethyl acetate: methanol = 19: 1); 1 H -NMR (DMSO-d 6): δ 2.16 (q, 2 H), 2.55 (s, 3 H), 2.64 (t, 2 H ), 4.04 (t, 2 H), 7.02 (d, 1 H), 7.11 (d, 2 H), 7.41-7.48 (m, 3 H), 7.64 (d, 2 H), 7.77 (dd, 1 H) ), 7.86 (s, 1 H), 8.11 (dd, 1 H), 8.06 (s, 1 H), 8.09 (d, 1 H), 8.44 (s, 1 H), 8.50 (d, 1 H), 9.21 (s, 1 H).

實施例84-11：1-[1-氧負離子基-2-苯基-5-(三氟甲基)-3-吡啶基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 84-11: 1-[1-oxanyl-2-phenyl-5-(trifluoromethyl)-3-pyridyl]-3-(2-{4-[2-(2- side) Oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.20(乙酸乙酯：甲醇=19：1)；1H-NMR(DMSO-d6)：δ 2.18(q，2 H)，2.64(t，2 H)，4.04(t，2 H)，7.21(d，2 H)，7.42-7.44(m，2 H)，7.57-7.59(m，3 H)，7.66(d，2 H)，7.86-7.89(m，2 H)，8.43(s，1 H)，8.57(s，1 H)，8.61(s，2 H)，9.55(s，1 H)。 TLC: Rf 0.20 (ethyl acetate: methanol = 19: 1); 1 H -NMR (DMSO-d 6): δ 2.18 (q, 2 H), 2.64 (t, 2 H), 4.04 (t, 2 H ), 7.21 (d, 2 H), 7.42-7.44 (m, 2 H), 7.57-7.59 (m, 3 H), 7.66 (d, 2 H), 7.86-7.89 (m, 2 H), 8.43 ( s, 1 H), 8.57 (s, 1 H), 8.61 (s, 2 H), 9.55 (s, 1 H).

實施例84-12：1-(6-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)-3-{5-(三氟甲基)-2-[6-(三氟甲基)-3-吡啶基]苯基}脲 Example 84-12: 1-(6-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-3-pyridyl )-3-{5-(trifluoromethyl)-2-[6-(trifluoromethyl)-3-pyridyl]phenyl}urea

TLC：Rf 0.53(己烷：乙酸乙酯=1：2)；1H-NMR(DMSO-d6)：δ 2.16(t，2 H)，2.64(t，2 H)，4.04(t，2 H)，7.00(d，1 H)，7.10(d，2 H)，7.54(s，2 H)，7.63(d，2 H)，7.86(s，1 H)，7.96(dd，1 H)，8.06(m，2 H)，8.20(m，2 H)，8.41(s，1 H)，8.85(d，1 H)，9.04(s，1 H)。 TLC: Rf 0.53 (hexane: ethyl acetate = 1: 2); 1 H -NMR (DMSO-d 6): δ 2.16 (t, 2 H), 2.64 (t, 2 H), 4.04 (t, 2 H), 7.00 (d, 1 H), 7.10 (d, 2 H), 7.54 (s, 2 H), 7.63 (d, 2 H), 7.86 (s, 1 H), 7.96 (dd, 1 H) , 8.06 (m, 2 H), 8.20 (m, 2 H), 8.41 (s, 1 H), 8.85 (d, 1 H), 9.04 (s, 1 H).

實施例84-13：1-[2-(6-甲基-3-吡啶基)-5-(三氟甲基)苯基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 84-13: 1-[2-(6-Methyl-3-pyridyl)-5-(trifluoromethyl)phenyl]-3-(2-{4-[2-(2- side) Oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.24(乙酸乙酯：甲醇=19：1)； 1H-NMR(DMSO-d6)：δ 2.16(q，2 H)，2.53(s，3 H)，2.64(t，2 H)，4.05(t，2 H)，7.21(d，2 H)，7.41-7.52(m，3 H)，7.67(d，2 H)，7.76(dd，1 H)，7.89(s，1 H)，8.19(s，1 H)，8.41(s，1 H)，8.50(d，1 H)，8.65(s，2 H)，9.27(s，1 H)。 TLC: Rf 0.24 (ethyl acetate:methanol = 19:1); 1 H-NMR (DMSO-d 6 ): δ 2.16 (q, 2 H), 2.53 (s, 3 H), 2.64 (t, 2 H) ), 4.05 (t, 2 H), 7.21 (d, 2 H), 7.41 - 7.52 (m, 3 H), 7.67 (d, 2 H), 7.76 (dd, 1 H), 7.89 (s, 1 H) ), 8.19 (s, 1 H), 8.41 (s, 1 H), 8.50 (d, 1 H), 8.65 (s, 2 H), 9.27 (s, 1 H).

實施例84-14：1-(6-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)-3-[5-(三氟甲基)-2，3’-二吡啶-3-基]脲 Example 84-14: 1-(6-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-3-pyridyl )-3-[5-(trifluoromethyl)-2,3'-dipyridin-3-yl]urea

TLC：Rf 0.15(乙酸乙酯：甲醇=19：1)；1H-NMR(DMSO-d6)：δ 2.16(q，2 H)，2.64(t，2 H)，4.04(t，2 H)，7.03(d，1 H)，7.12(d，2 H)，7.57-7.66(m，3 H)，7.98(s，1 H)，8.00(dd，1 H)，8.06-8.12(m，2 H)，8.45(s，1 H)，8.72(dd，1 H)，8.76(s，1 H)，8.78(s，1 H)，8.85(s，1 H)，9.28(s，1 H)。 TLC: Rf 0.15 (ethyl acetate:methanol = 19:1); 1 H-NMR (DMSO-d 6 ): δ 2.16 (q, 2 H), 2.64 (t, 2 H), 4.04 (t, 2 H) ), 7.03 (d, 1 H), 7.12 (d, 2 H), 7.57-7.66 (m, 3 H), 7.98 (s, 1 H), 8.00 (dd, 1 H), 8.06-8.12 (m, 2 H), 8.45 (s, 1 H), 8.72 (dd, 1 H), 8.76 (s, 1 H), 8.78 (s, 1 H), 8.85 (s, 1 H), 9.28 (s, 1 H) ).

實施例84-15：1-[2-(6-甲氧基-3-吡啶基)-5-(三氟甲基)苯基]-3-(6-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)脲 Example 84-15: 1-[2-(6-Methoxy-3-pyridyl)-5-(trifluoromethyl)phenyl]-3-(6-{4-[2-(2- Oxo-l-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-3-pyridyl)urea

TLC：Rf 0.54(己烷：乙酸乙酯=1：2)；1H-NMR(DMSO-d6)：δ 2.16(t，2 H)，2.64(t，2 H)，3.92(s，3 H)，4.04(t，2 H)，6.98(d，1 H)，7.03(d，1 H)，7.13(d，2 H)，7.43(d，2 H)，7.63(d，2 H)，7.78(dd，1 H)，7.86(s，1 H)，8.00(m，2 H)，8.10(d，1 H)，8.23(d，1 H)，8.45(s，1 H)，9.20(s，1 H)。 TLC: Rf 0.54 (hexane: ethyl acetate = 1: 2); 1 H -NMR (DMSO-d 6): δ 2.16 (t, 2 H), 2.64 (t, 2 H), 3.92 (s, 3 H), 4.04 (t, 2 H), 6.98 (d, 1 H), 7.03 (d, 1 H), 7.13 (d, 2 H), 7.43 (d, 2 H), 7.63 (d, 2 H) , 7.78 (dd, 1 H), 7.86 (s, 1 H), 8.00 (m, 2 H), 8.10 (d, 1 H), 8.23 (d, 1 H), 8.45 (s, 1 H), 9.20 (s, 1 H).

實施例84-16：1-[2-(3-羥基苯基)-5-(三氟甲基)-3-吡啶基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 84-16: 1-[2-(3-Hydroxyphenyl)-5-(trifluoromethyl)-3-pyridyl]-3-(2-{4-[2-(2- side oxygen) -ylpyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.31(甲醇：氯仿=1：19)；1H-NMR(DMSO-d6)：δ 2.10-2.22(m，2 H)，2.64(t，2 H)，4.01-4.08 (m，2H)，6.88-6.94(m，1 H)，6.97-7.06(m，2 H)，7.19-7.24(m，2 H)，7.35(t，1 H)，7.63-7.69(m，2 H)，7.89(s，1 H)，8.36(s，1 H)，8.66-8.70(m，3 H)，8.73-8.77(m，1 H)，9.53(s，1 H)，9.72(s，1 H)。 TLC: Rf 0.31 (methanol: chloroform = 1:19); 1 H-NMR (DMSO-d 6 ): δ 2.10-2.22 (m, 2 H), 2.64 (t, 2 H), 4.01-4.08 (m, 2H), 6.88-6.94 (m, 1 H), 6.97-7.06 (m, 2 H), 7.19-7.24 (m, 2 H), 7.35 (t, 1 H), 7.63-7.69 (m, 2 H) , 7.89(s,1 H), 8.36(s,1 H), 8.66-8.70(m,3 H),8.73-8.77(m,1 H),9.53(s,1 H),9.72(s,1 H).

實施例84-17：1-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[5-(三氟甲基)-2，3’-二吡啶-3-基]脲 Example 84-17: 1-(2-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl )-3-[5-(trifluoromethyl)-2,3'-dipyridin-3-yl]urea

TLC：Rf 0.41(乙酸乙酯：甲醇=4：1)；1H-NMR(DMSO-d6)：δ 2.16(q，2 H)，2.64(t，2 H)，4.05(t，2 H)，7.21(d，2 H)，7.56-7.60(m，1 H)，7.66(d，2 H)，7.89(s，1 H)，8.04-8.10(m，1 H)，8.59(s，1 H)，8.66(s，2 H)，8.72(dd，1 H)，8.74-8.79(m，2 H)，8.83-8.84(m，1 H)，9.34(s，1 H)。 TLC: Rf 0.41 (ethyl acetate:methanol = 4:1); 1 H-NMR (DMSO-d 6 ): δ 2.16 (q, 2 H), 2.64 (t, 2 H), 4.05 (t, 2 H) ), 7.21 (d, 2 H), 7.56-7.60 (m, 1 H), 7.66 (d, 2 H), 7.89 (s, 1 H), 8.04-8.10 (m, 1 H), 8.59 (s, 1 H), 8.66 (s, 2 H), 8.72 (dd, 1 H), 8.74 - 8.79 (m, 2 H), 8.83 - 8.84 (m, 1 H), 9.34 (s, 1 H).

實施例84-18：1-[2-(1-氧負離子基-4-吡啶基)-5-(三氟甲基)苯基]-3-(6-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)脲 Example 84-18: 1-[2-(1-oxanyloxy-4-pyridyl)-5-(trifluoromethyl)phenyl]-3-(6-{4-[2-(2- Oxo-l-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-3-pyridyl)urea

TLC：Rf 0.59(氯仿：甲醇=9：1)；1H-NMR(DMSO-d6)：δ 2.16(q，2 H)，2.64(t，2 H)，4.04(t，2 H)，7.03(d，1 H)，7.12(d，2 H)，7.56-7.53(m，4 H)，7.64(d，2 H)，7.87(s，1 H)，8.00(dd，1 H)，8.11-8.15(m，2 H)，8.32-8.41(m，3 H)，9.17(s，1 H)。 TLC: Rf 0.59 (chloroform:methanol = 9:1); 1 H-NMR (DMSO-d 6 ): δ 2.16 (q, 2 H), 2.64 (t, 2 H), 4.04 (t, 2 H), 7.03 (d, 1 H), 7.12 (d, 2 H), 7.56-7.53 (m, 4 H), 7.64 (d, 2 H), 7.87 (s, 1 H), 8.00 (dd, 1 H), 8.11-8.15 (m, 2 H), 8.32-8.41 (m, 3 H), 9.17 (s, 1 H).

實施例84-19：1-(6-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)-3-[4-(三氟甲基)-2-聯苯基]脲 Example 84-19: 1-(6-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-3-pyridyl )-3-[4-(trifluoromethyl)-2-biphenyl]urea

TLC：Rf 0.60(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 2.16(q，2 H)，2.64(t，2 H)，4.04(t，2 H)，7.02(d，1 H)，7.11(d，2 H)，7.39-7.56(m，7 H)，7.64(d，2 H)， 7.86(s，1 H)，7.95(s，1 H)，8.00(dd，1 H)，8.10(d，1 H)，8.43(s，1 H)，9.31(s，1 H)。 TLC: Rf 0.60 (ethyl acetate); 1 H-NMR (DMSO -d 6): δ 2.16 (q, 2 H), 2.64 (t, 2 H), 4.04 (t, 2 H), 7.02 (d, 1 H), 7.11 (d, 2 H), 7.39-7.56 (m, 7 H), 7.64 (d, 2 H), 7.86 (s, 1 H), 7.95 (s, 1 H), 8.00 (dd, 1 H), 8.10 (d, 1 H), 8.43 (s, 1 H), 9.31 (s, 1 H).

實施例84-20：1-[2-(4-羥基苯基)-5-(三氟甲基)-3-吡啶基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 84-20: 1-[2-(4-Hydroxyphenyl)-5-(trifluoromethyl)-3-pyridyl]-3-(2-{4-[2-(2- side oxygen) -ylpyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.68(乙酸乙酯：甲醇=19：1)；1H-NMR(DMSO-d6)：δ 2.16(q，2 H)，2.64(t，2 H)，4.05(t，2 H)，6.92(d，2 H)，7.21(d，2 H)，7.50(d，2 H)，7.67(d，2 H)，7.89(s，1 H)，8.37(s，1 H)，8.65(s，1 H)，8.67(s，2 H)，8.71(s，1 H)，9.49(s，1 H)，9.88(s，1 H)。 TLC: Rf 0.68 (ethyl acetate:methanol = 19:1); 1 H-NMR (DMSO-d 6 ): δ 2.16 (q, 2 H), 2.64 (t, 2 H), 4.05 (t, 2 H) ), 6.92 (d, 2 H), 7.21 (d, 2 H), 7.50 (d, 2 H), 7.67 (d, 2 H), 7.89 (s, 1 H), 8.37 (s, 1 H), 8.65 (s, 1 H), 8.67 (s, 2 H), 8.71 (s, 1 H), 9.49 (s, 1 H), 9.88 (s, 1 H).

實施例84-21：1-[2-(1-氧負離子基-4-吡啶基)-5-(三氟甲基)苯基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 84-21:1-[2-(1-oxoanion-4-pyridyl)-5-(trifluoromethyl)phenyl]-3-(2-{4-[2-(2-) Oxo-l-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.42(乙酸乙酯：甲醇：氨水=9：1：0.5)；1H-NMR(DMSO-d6)：δ 2.16(q，2 H)，2.64(t，2 H)，4.05(t，2 H)，7.21(d，2 H)，7.50-7.52(m，4 H)，7.66(d，2 H)，7.89(s，1 H)，8.27(s，1 H)，8.32-8.36(m，3 H)，8.66(s，2 H)，9.20(s，1 H)。 TLC: Rf 0.42 (ethyl acetate:methanol:methanol = 9:1: 0.5); 1 H-NMR (DMSO-d 6 ): δ 2.16 (q, 2 H), 2.64 (t, 2 H), 4.05 ( t,2 H), 7.21 (d, 2 H), 7.50-7.52 (m, 4 H), 7.66 (d, 2 H), 7.89 (s, 1 H), 8.27 (s, 1 H), 8.32 8.36 (m, 3 H), 8.66 (s, 2 H), 9.20 (s, 1 H).

實施例84-22：1-[2-(1-氧負離子基-3-吡啶基)-5-(三氟甲基)苯基]-3-(6-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)脲 Example 84-22: 1-[2-(1-Oxo-n-yl-3-pyridyl)-5-(trifluoromethyl)phenyl]-3-(6-{4-[2-(2- Oxo-l-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-3-pyridyl)urea

TLC：Rf 0.38(乙酸乙酯：甲醇：氨水=9：1：0.5)；1H-NMR(DMSO-d6)：δ 2.16(q，2 H)，2.64(t，2 H)，4.04(t，2 H)，7.03(d，1 H)，7.11(d，2 H)，7.38(d，1 H)，7.49-7.58(m，3 H)，7.64(d，2 H)，7.86(s，1 H)，8.00(dd，1 H)，8.11(d，1 H)，8.14 (s，1 H)，8.30-8.33(m，2 H)，8.44(s，1 H)，9.15(s，1 H)。 TLC: Rf 0.38 (ethyl acetate:methanol:methanol = 9:1: 0.5); 1 H-NMR (DMSO-d 6 ): δ 2.16 (q, 2 H), 2.64 (t, 2 H), 4.04 ( t, 2 H), 7.03 (d, 1 H), 7.11 (d, 2 H), 7.38 (d, 1 H), 7.49-7.58 (m, 3 H), 7.64 (d, 2 H), 7.86 ( s, 1 H), 8.00 (dd, 1 H), 8.11 (d, 1 H), 8.14 (s, 1 H), 8.30-8.33 (m, 2 H), 8.44 (s, 1 H), 9.15 ( s, 1 H).

實施例84-23：1-[2-(1-氧負離子基-3-吡啶基)-5-(三氟甲基)苯基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 84-23: 1-[2-(1-oxanyl-3-pyridyl)-5-(trifluoromethyl)phenyl]-3-(2-{4-[2-(2- Oxo-l-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.34(乙酸乙酯：甲醇：氨水=9：1：0.5)；1H-NMR(DMSO-d6)：δ 2.16(q，2 H)，2.64(t，2 H)，4.05(t，2 H)，7.22(d，2 H)，7.36-7.39(m，1 H)，7.51-7.57(m，3 H)，7.67(d，2 H)，7.90(s，1 H)，8.28-8.33(m，3 H)，8.41(s，1 H)，8.66(s，2 H)，9.23(s，1 H)。 TLC: Rf 0.34 (ethyl acetate:methanol:methanol = 9:1:0.5); 1 H-NMR (DMSO-d 6 ): δ 2.16 (q, 2 H), 2.64 (t, 2 H), 4.05 ( t,2 H), 7.22 (d, 2 H), 7.36-7.39 (m, 1 H), 7.51-7.57 (m, 3 H), 7.67 (d, 2 H), 7.90 (s, 1 H), 8.28-8.33 (m, 3 H), 8.41 (s, 1 H), 8.66 (s, 2 H), 9.23 (s, 1 H).

實施例84-24：1-[2-(2-甲氧基苯基)-5-(三氟甲基)-3-吡啶基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 84-24: 1-[2-(2-Methoxyphenyl)-5-(trifluoromethyl)-3-pyridyl]-3-(2-{4-[2-(2- Oxo-l-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.54(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 2.16(t，2 H)，2.64(t，2 H)，3.75(s，3 H)，4.05(t，2 H)，7.14(t，1 H)，7.21(m，3 H)，7.37(dd，1 H)，7.55(dt，1 H)，7.66(d，2 H)，7.89(s，2 H)，8.67(s，3 H)，8.77(d，1 H)，9.61(s，1 H)。 TLC: Rf 0.54 (ethyl acetate); 1 H-NMR (DMSO -d 6): δ 2.16 (t, 2 H), 2.64 (t, 2 H), 3.75 (s, 3 H), 4.05 (t, 2 H), 7.14 (t, 1 H), 7.21 (m, 3 H), 7.37 (dd, 1 H), 7.55 (dt, 1 H), 7.66 (d, 2 H), 7.89 (s, 2 H) ), 8.67 (s, 3 H), 8.77 (d, 1 H), 9.61 (s, 1 H).

實施例84-25：1-[2-(3-甲氧基苯基)-5-(三氟甲基)-3-吡啶基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 84-25: 1-[2-(3-Methoxyphenyl)-5-(trifluoromethyl)-3-pyridyl]-3-(2-{4-[2-(2- Oxo-l-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.43(己烷：乙酸乙酯=1：2)；1H-NMR(DMSO-d6)：δ 2.16(t，2 H)，2.64(t，2 H)，3.81(s，3 H)，4.05(t，2 H)，7.08(d，1 H)，7.19(m，4 H)，7.48(t，1 H)，7.66(d，2 H)，7.90(s，1 H)，8.38(s，1 H)，8.67(s，2 H)，8.71(s，1 H)， 8.79(s，1 H)，9.52(s，1 H)。 TLC: Rf 0.43 (hexane: ethyl acetate = 1: 2); 1 H -NMR (DMSO-d 6): δ 2.16 (t, 2 H), 2.64 (t, 2 H), 3.81 (s, 3 H), 4.05 (t, 2 H), 7.08 (d, 1 H), 7.19 (m, 4 H), 7.48 (t, 1 H), 7.66 (d, 2 H), 7.90 (s, 1 H) , 8.38 (s, 1 H), 8.67 (s, 2 H), 8.71 (s, 1 H), 8.79 (s, 1 H), 9.52 (s, 1 H).

實施例84-26：1-[2-(2-羥基苯基)-5-(三氟甲基)-3-吡啶基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 84-26: 1-[2-(2-Hydroxyphenyl)-5-(trifluoromethyl)-3-pyridyl]-3-(2-{4-[2-(2- side oxygen) -ylpyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.53(己烷：乙酸乙酯=1：2)；1H-NMR(DMSO-d6)：δ 2.16(t，2 H)，2.64(t，2 H)，4.05(t，2 H)，7.00(m，2 H)，7.21(d，2 H)，7.30-7.34(m，2 H)，7.67(d，2 H)，7.89(s，1 H)，8.04(br，1 H)，8.65(s，1 H)，8.67(s，2 H)，8.76(d，1 H)，9.75(s，1 H)，10.2(br s，1 H)。 TLC: Rf 0.53 (hexane: ethyl acetate = 1: 2); 1 H -NMR (DMSO-d 6): δ 2.16 (t, 2 H), 2.64 (t, 2 H), 4.05 (t, 2 H), 7.00 (m, 2 H), 7.21 (d, 2 H), 7.30-7.34 (m, 2 H), 7.67 (d, 2 H), 7.89 (s, 1 H), 8.04 (br, 1) H), 8.65 (s, 1 H), 8.67 (s, 2 H), 8.76 (d, 1 H), 9.75 (s, 1 H), 10.2 (br s, 1 H).

實施例84-27：1-(1-氧負離子基-6-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)-3-[2-苯基-5-(三氟甲基)-3-吡啶基]脲 Example 84-27: 1-(1-oxoanion-6-{4-[2-(2-o-oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy }-3-pyridyl)-3-[2-phenyl-5-(trifluoromethyl)-3-pyridyl]urea

TLC：Rf 0.44(乙酸乙酯：甲醇：氨水=9：1：0.5)；1H-NMR(DMSO-d6)：δ 2.15(q，2 H)，2.63(t，2 H)，4.02(t，2 H)，6.93(d，2 H)，7.27(dd，1 H)，7.35(d，1 H)，7.55-7.69(m，7 H)，7.84(s，1 H)，8.47(s，1 H)，8.66(d，1 H)，8.70(s，1 H)，8.75(s，1 H)，9.73(s，1 H)。 TLC: Rf 0.44 (ethyl acetate:methanol:methanol = 9:1:0.5); 1 H-NMR (DMSO-d 6 ): δ 2.15 (q, 2 H), 2.63 (t, 2 H), 4.02 ( t,2 H), 6.93 (d, 2 H), 7.27 (dd, 1 H), 7.35 (d, 1 H), 7.55-7.69 (m, 7 H), 7.84 (s, 1 H), 8.47 ( s, 1 H), 8.66 (d, 1 H), 8.70 (s, 1 H), 8.75 (s, 1 H), 9.73 (s, 1 H).

實施例84-28：1-[2-(4-甲氧基苯基)-5-(三氟甲基)-3-吡啶基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 84-28: 1-[2-(4-Methoxyphenyl)-5-(trifluoromethyl)-3-pyridyl]-3-(2-{4-[2-(2- Oxo-l-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.56(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 2.15(q，2 H)，2.64(t，2 H)，3.80(s，3 H)，4.05(t，2 H)，7.11(d，2 H)，7.22(d，2 H)，7.60-7.69(m，4 H)，7.90(s，1 H)，8.41(s，1 H)，8.68-8.73(m，4 H)，9.47(s，1 H)。 TLC: Rf 0.56 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 2.15 (q, 2 H), 2.64 (t, 2 H), 3.80 (s, 3 H), 4.05 (t, 2 H), 7.11 (d, 2 H), 7.22 (d, 2 H), 7.60-7.69 (m, 4 H), 7.90 (s, 1 H), 8.41 (s, 1 H), 8.68-8.73 ( m, 4 H), 9.47 (s, 1 H).

實施例84-29：1-[2-({6-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]-3-吡啶基}氧基)-5-嘧啶基]-3-[2-苯基-5-(三氟甲基)-3-吡啶基]脲 Example 84-29: 1-[2-({6-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]-3-pyridyl}oxy )-5-pyrimidinyl]-3-[2-phenyl-5-(trifluoromethyl)-3-pyridyl]urea

TLC：Rf 0.20(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 2.19(t，2 H)，2.35(t，2 H)，4.14(t，2 H)，7.26(d，1 H)，7.30(m，3 H)，7.52(dd，1 H)，7.58-7.62(m，2 H)，7.75(s，1 H)，7.81(s，1 H)，8.21(d，1 H)，8.39(s，1 H)，8.60(s，1 H)，8.71(s，2 H)，8.84(s，1 H)。 TLC: Rf 0.20 (ethyl acetate); 1 H-NMR (DMSO -d 6): δ 2.19 (t, 2 H), 2.35 (t, 2 H), 4.14 (t, 2 H), 7.26 (d, 1 H), 7.30 (m, 3 H), 7.52 (dd, 1 H), 7.58-7.62 (m, 2 H), 7.75 (s, 1 H), 7.81 (s, 1 H), 8.21 (d, 1 H), 8.39 (s, 1 H), 8.60 (s, 1 H), 8.71 (s, 2 H), 8.84 (s, 1 H).

實施例84-30：1-[2-環己基-5-(三氟甲基)-3-吡啶基]-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 84-30: 1-[2-Cyclohexyl-5-(trifluoromethyl)-3-pyridyl]-3-(2-{4-[2-(2- oxo-l-piperidine) Pyridyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.64(己烷：乙酸乙酯=1：4)；1H-NMR(DMSO-d6)：δ 1.20-1.99(m，14 H)，2.61(t，2 H)，3.00(m，1 H)，4.07(t，2 H)，7.23(d，2 H)，7.66(d，2 H)，7.91(s，1 H)，8.49-8.50(m，1 H)，8.60(s，2 H)，8.74(s，2 H)，9.33(s，1 H)。 TLC: Rf 0.64 (hexane: ethyl acetate = 1 : 4); 1 H-NMR (DMSO-d 6 ): δ 1.20-1.99 (m, 14 H), 2.61 (t, 2 H), 3.00 (m) , 1 H), 4.07 (t, 2 H), 7.23 (d, 2 H), 7.66 (d, 2 H), 7.91 (s, 1 H), 8.49-8.50 (m, 1 H), 8.60 (s) , 2 H), 8.74 (s, 2 H), 9.33 (s, 1 H).

實施例84-31：1-[1-(2，3-二氫-1H-茚-5-基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]-3-(4-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}苯基)脲 Example 84-31:1-[1-(2,3-Dihydro-1H-indol-5-yl)-3-(2-methyl-2-propyl)-1H-pyrazole-5-yl ]-3-(4-{4-[2-(2-Sideoxy-1-piperidyl)-1,3-thiazol-5-yl]phenoxy}phenyl)urea

TLC：Rf 0.56(己烷：乙酸乙酯=4：6)；1H-NMR(DMSO-d6)：δ 1.25(s，9 H)，1.78-1.98(m，4 H)，2.06(q，2 H)，2.59(t，2 H)，2.85-2.95(m，4 H)，4.05(t，2 H)，6.33(s，1 H)，6.94-7.02(m，4 H)，7.19-7.24(m，1 H)，7.29-7.38(m，2 H)，7.41(d，2 H)，7.58(d，2 H)，7.83(s，1 H)，8.29(s，1 H)，9.02(s，1 H)。 TLC: Rf 0.56 (hexane: ethyl acetate = 4: 6); 1 H-NMR (DMSO-d 6 ): δ 1.25 (s, 9 H), 1.78-1.98 (m, 4 H), 2.06 (q) , 2 H), 2.59 (t, 2 H), 2.85-2.95 (m, 4 H), 4.05 (t, 2 H), 6.33 (s, 1 H), 6.94-7.02 (m, 4 H), 7.19 -7.24 (m, 1 H), 7.29-7.38 (m, 2 H), 7.41 (d, 2 H), 7.58 (d, 2 H), 7.83 (s, 1 H), 8.29 (s, 1 H) , 9.02 (s, 1 H).

實施例84-32：1-[3-(2-甲基-2-丙基)-1-苯基-1H-吡唑-5-基]-3-(6-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)脲 Example 84-32: 1-[3-(2-Methyl-2-propyl)-1-phenyl-1H-pyrazol-5-yl]-3-(6-{4-[2-( 2-sided oxy-1-piperidinyl)-1,3-thiazol-5-yl]phenoxy}-3-pyridyl)urea

TLC：Rf 0.59(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 1.26(s，9 H)，1.82-1.95(m，4 H)，2.60(t，2 H)，4.06(t，2 H)，6.36(s，1 H)，7.01(d，1 H)，7.10(dd，2 H)，7.29(m，1 H)，7.51(dd，4 H)，7.62(dd，2 H)，7.88(s，1 H)，7.95(dd，1 H)，8.12(d，1 H)，8.49(s，1 H)，9.12(s，1 H)。 TLC: Rf 0.59 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 1.26 (s, 9 H), 1.82-1.95 (m, 4 H), 2.60 (t, 2 H), 4.06 ( t,2 H), 6.36 (s, 1 H), 7.01 (d, 1 H), 7.10 (dd, 2 H), 7.29 (m, 1 H), 7.51 (dd, 4 H), 7.62 (dd, 2 H), 7.88 (s, 1 H), 7.95 (dd, 1 H), 8.12 (d, 1 H), 8.49 (s, 1 H), 9.12 (s, 1 H).

實施例84-33：1-(6-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)-3-[2-苯基-5-(三氟甲基)-3-吡啶基]脲 Example 84-33: 1-(6-{4-[2-(2-Sideoxy-1-piperidyl)-1,3-thiazol-5-yl]phenoxy}-3-pyridyl )-3-[2-phenyl-5-(trifluoromethyl)-3-pyridyl]urea

TLC：Rf 0.65(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 1.82-1.95(m，4 H)，2.61(t，2 H)，4.04(t，2 H)，7.04(d，1 H)，7.12(d，2 H)，7.53-7.67(m，7 H)，7.88(s，1 H)，8.00(dd，1 H)，8.10(d，1 H)，8.29(s，1 H)，8.70(s，1 H)，8.79 (s，1 H)，9.40(s，1 H)。 TLC: Rf 0.65 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 1.82-1.95 (m, 4 H), 2.61 (t, 2 H), 4.04 (t, 2 H), 7.04 ( d, 1 H), 7.12 (d, 2 H), 7.53-7.67 (m, 7 H), 7.88 (s, 1 H), 8.00 (dd, 1 H), 8.10 (d, 1 H), 8.29 ( s, 1 H), 8.70 (s, 1 H), 8.79 (s, 1 H), 9.40 (s, 1 H).

實施例84-34：1-(6-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)-3-[2-(4-吡啶基)-5-(三氟甲基)苯基]脲 Example 84-34: 1-(6-{4-[2-(2-Sideoxy-1-piperidinyl)-1,3-thiazol-5-yl]phenoxy}-3-pyridyl )-3-[2-(4-pyridyl)-5-(trifluoromethyl)phenyl]urea

TLC：Rf 0.27(乙酸乙酯：甲醇=19：1)；1H-NMR(DMSO-d6)：δ 1.82-1.98(m，4 H)，2.60(t，2 H)，4.06(t，2 H)，7.02(d，1 H)，7.11(d，2 H)，7.48-7.50(m，4 H)，7.63(d，2 H)，7.88(s，1 H)，7.98(dd，1 H)，8.09-8.11(m，2 H)，8.42(s，1 H)，8.72(d，2 H)，9.23(s，1 H)。 TLC: Rf 0.27 (ethyl acetate: methanol = 19: 1); 1 H -NMR (DMSO-d 6): δ 1.82-1.98 (m, 4 H), 2.60 (t, 2 H), 4.06 (t, 2 H), 7.02 (d, 1 H), 7.11 (d, 2 H), 7.48-7.50 (m, 4 H), 7.63 (d, 2 H), 7.88 (s, 1 H), 7.98 (dd, 1 H), 8.09-8.11 (m, 2 H), 8.42 (s, 1 H), 8.72 (d, 2 H), 9.23 (s, 1 H).

實施例84-35：1-(6-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)-3-[2-(3-吡啶基)-5-(三氟甲基)苯基]脲 Example 84-35: 1-(6-{4-[2-(2-Sideoxy-1-piperidinyl)-1,3-thiazol-5-yl]phenoxy}-3-pyridyl )-3-[2-(3-pyridyl)-5-(trifluoromethyl)phenyl]urea

TLC：Rf 0.51(乙酸乙酯：甲醇=19：1)；1H-NMR(DMSO-d6)：δ 1.81-2.00(m，4 H)，2.60(t，2 H)，4.06(t，2 H)，7.01(d，1 H)，7.10(d，2 H)，7.40-7.50(m，2 H)，7.56(dd，1 H)，7.62(d，2 H)，7.87-7.90(m，2 H)，7.97(dd，1 H)，8.08(d，1 H)，8.11(s，1 H)，8.41(s，1 H)，8.63-8.67(m，2 H)，9.21(s，1 H)。 TLC: Rf 0.51 (ethyl acetate:methanol = 19:1); 1 H-NMR (DMSO-d 6 ): δ 1.81-2.00 (m, 4 H), 2.60 (t, 2 H), 4.06 (t, 2 H), 7.01 (d, 1 H), 7.10 (d, 2 H), 7.40-7.50 (m, 2 H), 7.56 (dd, 1 H), 7.62 (d, 2 H), 7.87-7.90 ( m, 2 H), 7.97 (dd, 1 H), 8.08 (d, 1 H), 8.11 (s, 1 H), 8.41 (s, 1 H), 8.63 - 8.67 (m, 2 H), 9.21. s, 1 H).

實施例84-36：1-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[5-(三氟甲基)-2，4’-二吡啶-3-基]脲 Example 84-36: 1-(2-{4-[2-(2-Sideoxy-1-piperidyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl )-3-[5-(trifluoromethyl)-2,4'-dipyridin-3-yl]urea

TLC：Rf 0.19(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 1.82-1.98(m，4 H)，2.61(t，2 H)，4.07(t，2 H)，7.22(d，2 H)，7.67(m，4 H)，7.91(s，1 H)，8.65(br s，1 H)，8.67(s，2 H)，8.76(m，4 H)，9.35(br s，1 H)。 TLC: Rf 0.19 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 1.82-1.98 (m, 4 H), 2.61 (t, 2 H), 4.07 (t, 2 H), 7.22 ( d, 2 H), 7.67 (m, 4 H), 7.91 (s, 1 H), 8.65 (br s, 1 H), 8.67 (s, 2 H), 8.76 (m, 4 H), 9.35 (br) s, 1 H).

實施例84-37：1-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-(3-吡啶基)-5-(三氟甲基)苯基]脲 Example 84-37: 1-(2-{4-[2-(2-Sideoxy-1-piperidyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl )-3-[2-(3-pyridyl)-5-(trifluoromethyl)phenyl]urea

TLC：Rf 0.53(乙酸乙酯：甲醇=19：1)；1H-NMR(DMSO-d6)：δ 1.80-2.00(m，4 H)，2.61(t，2 H)，4.07(t，2 H)，7.21(d，2 H)，7.47-7.58(m，3 H)，7.66(d，2 H)，7.82-7.91(m，2 H)，8.24(s，1 H)，8.38(s，1 H)，8.64-8，68(m，4 H)，9.24(s，1 H)。 TLC: Rf 0.53 (ethyl acetate: methanol = 19: 1); 1 H -NMR (DMSO-d 6): δ 1.80-2.00 (m, 4 H), 2.61 (t, 2 H), 4.07 (t, 2 H), 7.21 (d, 2 H), 7.47-7.58 (m, 3 H), 7.66 (d, 2 H), 7.82-7.91 (m, 2 H), 8.24 (s, 1 H), 8.38 ( s, 1 H), 8.64-8, 68 (m, 4 H), 9.24 (s, 1 H).

實施例84-38：1-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[5-(三氟甲基)-2，3’-二吡啶-3-基]脲 Example 84-38: 1-(2-{4-[2-(2-Sideoxy-1-piperidyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl )-3-[5-(trifluoromethyl)-2,3'-dipyridin-3-yl]urea

TLC：Rf 0.16(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 1.82-1.94(m，4 H)，2.61(t，2 H)，4.07(t，2 H)，7.22(d，2 H)，7.57(dd，1 H)，7.65(d，2 H)，7.91(s，1 H)，8.08(d，1 H)，8.61(br s，1 H)，8.66(s，2 H)，8.71(dd，1 H)，8.76(d，2 H)，8.85(d，1 H)，9.35(br s，1 H)。 TLC: Rf 0.16 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 1.82-1.94 (m, 4 H), 2.61 (t, 2 H), 4.07 (t, 2 H), 7.22 ( d, 2 H), 7.57 (dd, 1 H), 7.65 (d, 2 H), 7.91 (s, 1 H), 8.08 (d, 1 H), 8.61 (br s, 1 H), 8.66 (s) , 2 H), 8.71 (dd, 1 H), 8.76 (d, 2 H), 8.85 (d, 1 H), 9.35 (br s, 1 H).

實施例84-39：1-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-(4-吡啶基)-5-(三氟甲基)苯基]脲 Example 84-39: 1-(2-{4-[2-(2-Sideoxy-1-piperidyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl )-3-[2-(4-pyridyl)-5-(trifluoromethyl)phenyl]urea

TLC：Rf 0.32(乙酸乙酯：甲醇=19：1)；1H-NMR(DMSO-d6)：δ 1.80-1.98(m，4 H)，2.61(t，2 H)，4.07(t，2 H)，7.21(d，2 H)，7.46-7.56(m，4 H)，7.66(d，2 H)，7.91(s，1 H)，8.23(s，1 H)，8.38(s，1 H)，8.64(s，2 H)，8.72(d，2 H)，9.23(s，1 H)。 TLC: Rf 0.32 (ethyl acetate: methanol = 19: 1); 1 H -NMR (DMSO-d 6): δ 1.80-1.98 (m, 4 H), 2.61 (t, 2 H), 4.07 (t, 2 H), 7.21 (d, 2 H), 7.46-7.56 (m, 4 H), 7.66 (d, 2 H), 7.91 (s, 1 H), 8.23 (s, 1 H), 8.38 (s, 1 H), 8.64 (s, 2 H), 8.72 (d, 2 H), 9.23 (s, 1 H).

實施例84-40：1-[2-(6-甲基-3-吡啶基)-5-(三氟甲基)苯基]-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 84-40: 1-[2-(6-Methyl-3-pyridyl)-5-(trifluoromethyl)phenyl]-3-(2-{4-[2-(2- side) Oxy-1-piperidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.66(乙酸乙酯：甲醇=19：1)；1H-NMR(DMSO-d6)：δ 1.75-2.00(m，4 H)，2.55(s，3 H)，2.61(t， 2 H)，4.07(t，2 H)，7.21(d，2 H)，7.41-7.52(m，3 H)，7.66(d，2 H)，7.75-7.78(m，1 H)，7.91(s，1 H)，8.19(s，1 H)，8.41(s，1 H)，8.50(s，1 H)，8.65(s，2 H)，9.27(s，1 H)。 TLC: Rf 0.66 (ethyl acetate: methanol = 19: 1); 1 H -NMR (DMSO-d 6): δ 1.75-2.00 (m, 4 H), 2.55 (s, 3 H), 2.61 (t, 2 H), 4.07 (t, 2 H), 7.21 (d, 2 H), 7.41-7.52 (m, 3 H), 7.66 (d, 2 H), 7.75-7.78 (m, 1 H), 7.91 ( s, 1 H), 8.19 (s, 1 H), 8.41 (s, 1 H), 8.50 (s, 1 H), 8.65 (s, 2 H), 9.27 (s, 1 H).

實施例84-41：1-[2-異丙基-5-(三氟甲基)-3-吡啶基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 84-41:1-[2-Isopropyl-5-(trifluoromethyl)-3-pyridyl]-3-(2-{4-[2-(2-Sideoxy-1-) Pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.59(二氯甲烷：乙酸乙酯：甲醇=8：4：1)；1H-NMR(DMSO-d6)：δ 1.23(d，6 H)，2.10-2.23(m，2 H)，2.64(t，2 H)，3.30-3.45(m，1 H)，4.05(t，2 H)，7.24(d，2 H)，7.68(d，2 H)，7.89(s，1 H)，8.52-8.56(m，1 H)，8.63(d，2 H)，8.74(s，2 H)，9.34(s，1 H)。 TLC: Rf 0.59 (dichloromethane: ethyl acetate:methanol = 8:4:1); 1 H-NMR (DMSO-d 6 ): δ 1.23 (d, 6 H), 2.10-2.23 (m, 2 H) ), 2.64 (t, 2 H), 3.30-3.45 (m, 1 H), 4.05 (t, 2 H), 7.24 (d, 2 H), 7.68 (d, 2 H), 7.89 (s, 1 H) ), 8.52 - 8.56 (m, 1 H), 8.63 (d, 2 H), 8.74 (s, 2 H), 9.34 (s, 1 H).

實施例84-42：1-[2-異丙基-5-(三氟甲基)-3-吡啶基]-3-(2-{4-[2-(2-側氧基-1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 84-42: 1-[2-Isopropyl-5-(trifluoromethyl)-3-pyridyl]-3-(2-{4-[2-(2-Sideoxy-1-) Piperidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.40(己烷：乙酸乙酯=1：4)；1H-NMR(DMSO-d6)：δ 1.24(d，6 H)，1.83-1.98(m，4 H)，2.61(t，2 H)，3.34(m，1 H)，4.07(t，2 H)，7.23(d，2 H)，7.67(d，2 H)，7.92(s，1 H)，8.55(s，1 H)，8.62(s，1 H)，8.70(s，1 H)，8.74(s，2 H)，9.43(s，1 H)。 TLC: Rf 0.40 (hexane: ethyl acetate = 1 : 4); 1 H-NMR (DMSO-d 6 ): δ 1.24 (d, 6 H), 1.83-1.98 (m, 4 H), 2.61 (t) , 2 H), 3.34 (m, 1 H), 4.07 (t, 2 H), 7.23 (d, 2 H), 7.67 (d, 2 H), 7.92 (s, 1 H), 8.55 (s, 1) H), 8.62 (s, 1 H), 8.70 (s, 1 H), 8.74 (s, 2 H), 9.43 (s, 1 H).

實施例85 Example 85

使用相當之胺衍生物替代實施例5製造之化合物，使用相當 之胺基甲酸酯衍生物替代實施例8製造之化合物，進行與實施例9相同之操作，獲得具有以下物性值之本發明化合物。或使用相當之5-溴噻唑衍生物替代實施例18製造之化合物，使用相當之硼酸酯衍生物替代實施例20製造之化合物，進行與實施例21相同之操作，獲得具有以下物性值之本發明化合物。 Substituting the amine compound for the compound produced in Example 5, using equivalent The urethane derivative was replaced with the compound produced in Example 8, and the same operation as in Example 9 was carried out to obtain a compound of the present invention having the following property values. Alternatively, the compound produced in Example 18 was replaced with a corresponding 5-bromothiazole derivative, and the compound produced in Example 20 was replaced with a corresponding boronic acid ester derivative, and the same operation as in Example 21 was carried out to obtain a material having the following physical properties. Inventive compound.

實施例85-1：磷酸二氫3-[3-{[(2{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-嘧啶基]胺基甲醯基}胺基)-5-(三氟甲基)-2-吡啶基]苯基 Example 85-1: 3-[3-{[(2{4-[2-(2-Sideoxy-1-pyrrolidyl)-1,3-thiazol-5-pyrimidinyl]amine dihydrogen phosphate Methyl hydrazino}amino)-5-(trifluoromethyl)-2-pyridyl]phenyl

TLC：Rf 0.23(乙酸乙酯：乙酸：水=6：1：1)；1H-NMR(DMSO-d6)：δ 2.11-2.21(m，2 H)，2.61-2.67(m，2 H)，4.05(t，2 H)，7.19-7.25(m，2 H)，7.28-7.33(m，1 H)，7.41-7.57(m，3 H)，7.64-7.70(m，2 H)，7.90(s，1 H)，8.49(s，1 H)，8.68(s，2 H)，8.72-8.78(m，2 H)，9.45(s，1 H)。 TLC: Rf 0.23 (ethyl acetate: acetic acid: water = 6:1:1); 1 H-NMR (DMSO-d 6 ): δ 2.11-2.21 (m, 2 H), 2.61-2.67 (m, 2 H) ), 4.05 (t, 2 H), 7.19-7.25 (m, 2 H), 7.28-7.33 (m, 1 H), 7.41-7.57 (m, 3 H), 7.64-7.70 (m, 2 H), 7.90 (s, 1 H), 8.49 (s, 1 H), 8.68 (s, 2 H), 8.72-8.78 (m, 2 H), 9.45 (s, 1 H).

實施例85-2：1-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[3-(三氟甲基)苯基]脲 Example 85-2: 1-(2-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl )-3-[3-(trifluoromethyl)phenyl]urea

TLC：Rf 0.26(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 2.11-2.23(m，2 H)，2.64(t，2 H)，4.05(t，2 H)，7.23(d，2 H)，7.33(dd，1 H)，7.51(t，1 H)，7.62(dd，1 H)，7.68(d，2 H)，7.90(s，1 H)，7.97(s，1 H)，8.73(s，2 H)，8.98(s，1 H)，9.31(s，1 H)。 TLC: Rf 0.26 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 2.11-2.23 (m, 2 H), 2.64 (t, 2 H), 4.05 (t, 2 H), 7.23 ( d, 2 H), 7.33 (dd, 1 H), 7.51 (t, 1 H), 7.62 (dd, 1 H), 7.68 (d, 2 H), 7.90 (s, 1 H), 7.97 (s, 1 H), 8.73 (s, 2 H), 8.98 (s, 1 H), 9.31 (s, 1 H).

實施例85-3：1-[6-({6-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]-3-吡啶基}氧基)-3-吡啶基]-3-[2-苯基-5-(三氟甲基)-3-吡啶基]脲 Example 85-3: 1-[6-({6-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]-3-pyridyl}oxy )-3-pyridyl]-3-[2-phenyl-5-(trifluoromethyl)-3-pyridyl]urea

TLC：Rf 0.66(乙酸乙酯：甲醇=9：1)；1H-NMR(DMSO-d6)：δ 2.13-2.27(m，2 H)，2.64(t，2 H)，4.05(t，2 H)，7.19(d，1 H)，7.53-7.67(m，6 H)，7.98(d，1 H)，8.04(dd，1 H)，8.09(d，1 H)，8.15(s，1 H)，8.29(s，1 H)，8.37(d，1 H)，8.70(s，1 H)，8.78(s，1 H)，9.42(s，1 H)。 TLC: Rf 0.66 (ethyl acetate: methanol = 9: 1); 1 H -NMR (DMSO-d 6): δ 2.13-2.27 (m, 2 H), 2.64 (t, 2 H), 4.05 (t, 2 H), 7.19 (d, 1 H), 7.53-7.67 (m, 6 H), 7.98 (d, 1 H), 8.04 (dd, 1 H), 8.09 (d, 1 H), 8.15 (s, 1 H), 8.29 (s, 1 H), 8.37 (d, 1 H), 8.70 (s, 1 H), 8.78 (s, 1 H), 9.42 (s, 1 H).

實施例85-4：1-[2-(4-{2-[(4S)-4-羥基-2-側氧基-1-吡咯啶基]-1，3-噻唑-5-基}苯氧基)-5-嘧啶基]-3-[2-苯基-5-(三氟甲基)-3-吡啶基]脲 Example 85-4: 1-[2-(4-{2-[(4S)-4-hydroxy-2-oxo-l-pyrrolidinyl]-1,3-thiazol-5-yl}benzene Oxy)-5-pyrimidinyl]-3-[2-phenyl-5-(trifluoromethyl)-3-pyridyl]urea

TLC：Rf 0.20(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 2.38-2.50(m，1 H)，2.99(dd，1 H)，3.95(d，1 H)，4.14(dd，1 H)，4.45-4.53(m，1 H)，5.49(d，1 H)，7.19-7.25(m，2 H)，7.49-7.60(m，3 H)，7.63-7.70(m，4 H)，7.89(s，1 H)，8.42(s，1 H)，8.67(s，2 H)，8.71-8.78(m，2 H)，9.47(s，1 H)。 TLC: Rf 0.20 (ethyl acetate); 1 H-NMR (DMSO -d 6): δ 2.38-2.50 (m, 1 H), 2.99 (dd, 1 H), 3.95 (d, 1 H), 4.14 ( Dd,1 H), 4.45-4.53 (m, 1 H), 5.49 (d, 1 H), 7.19-7.25 (m, 2 H), 7.49-7.60 (m, 3 H), 7.63-7.70 (m, 4 H), 7.89 (s, 1 H), 8.42 (s, 1 H), 8.67 (s, 2 H), 8.71 - 8.78 (m, 2 H), 9.47 (s, 1 H).

實施例85-5：1-(2-{2-氟-4-[2-(2-側氧基-1-吡咯啶基)-1，3- 噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-苯基-5-(三氟甲基)-3-吡啶基]脲 Example 85-5: 1-(2-{2-Fluoro-4-[2-(2-o-oxy-1-pyrrolidinyl)-1,3- Thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-[2-phenyl-5-(trifluoromethyl)-3-pyridyl]urea

TLC：Rf 0.50(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 2.11-2.23(m，2 H)，2.64(t，2 H)，4.09(t，2 H)，7.40-7.67(m，7 H)，7.75(dd，1 H)，7.99(s，1 H)，8.43(s，1 H)，8.67(s，2 H)，8.72(d，1 H)，8.74(d，1 H)，9.47(s，1 H)。 TLC: Rf 0.50 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 2.11-2.23 (m, 2 H), 2.64 (t, 2 H), 4.09 (t, 2 H), 7.40- 7.67 (m, 7 H), 7.75 (dd, 1 H), 7.99 (s, 1 H), 8.43 (s, 1 H), 8.67 (s, 2 H), 8.72 (d, 1 H), 8.74 ( d, 1 H), 9.47 (s, 1 H).

實施例85-6：1-(2-{2-氟-4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-(3-吡啶基)-5-(三氟甲基)苯基]脲 Example 85-6: 1-(2-{2-Fluoro-4-[2-(2-o-oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}- 5-pyrimidinyl)-3-[2-(3-pyridyl)-5-(trifluoromethyl)phenyl]urea

TLC：Rf 0.43(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 2.11-2.24(m，2 H)，2.64(t，2 H)，4.09(t，2 H)，7.37-7.51(m，5 H)，7.56(dd，1 H)，7.79(dd，1 H)，7.90(dt，1 H)，7.99(s，1 H)，8.25(s，1 H)，8.39(s，1 H)，8.64(s，2 H)，8.67(dd，1 H)，9.25(s，1 H)。 TLC: Rf 0.43 (ethyl acetate); 1 H-NMR (DMSO -d 6): δ 2.11-2.24 (m, 2 H), 2.64 (t, 2 H), 4.09 (t, 2 H), 7.37- 7.51 (m, 5 H), 7.56 (dd, 1 H), 7.79 (dd, 1 H), 7.90 (dt, 1 H), 7.99 (s, 1 H), 8.25 (s, 1 H), 8.39 ( s, 1 H), 8.64 (s, 2 H), 8.67 (dd, 1 H), 9.25 (s, 1 H).

實施例85-7：1-[2-氯-5-(三氟甲基)-3-吡啶基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 85-7: 1-[2-Chloro-5-(trifluoromethyl)-3-pyridyl]-3-(2-{4-[2-(2-o-oxy-1-pyrrolidine) -1,3-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.36(己烷：乙酸乙酯=1：2)；1H-NMR(DMSO-d6)：δ 2.10-2.24(m，2 H)，2.64(t，2 H)，4.05(t，2 H)，7.24(d，2 H)，7.68(d，2 H)，7.90(s，1 H)，8.49(s，1 H)，8.77(s，2 H)，8.87(s，1 H)，8.95(d，1 H)，9.78(s，1 H)。 TLC: Rf 0.36 (hexane: ethyl acetate = 1: 2); 1 H -NMR (DMSO-d 6): δ 2.10-2.24 (m, 2 H), 2.64 (t, 2 H), 4.05 (t , 2 H), 7.24 (d, 2 H), 7.68 (d, 2 H), 7.90 (s, 1 H), 8.49 (s, 1 H), 8.77 (s, 2 H), 8.87 (s, 1) H), 8.95 (d, 1 H), 9.78 (s, 1 H).

實施例85-8：1-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[5-(三氟甲基)-3-吡啶基]脲 Example 85-8: 1-(2-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl )-3-[5-(trifluoromethyl)-3-pyridyl]urea

TLC：Rf 0.54(己烷：乙酸乙酯=1：2)；1H-NMR(DMSO-d6)：δ 2.11-2.24(m，2 H)，2.64(t，2 H)，4.05(t，2 H)，7.24(d，2 H)，7.68(d，2 H)，7.90(s，1 H)，8.39(s，1 H)，8.57(s，1 H)，8.73(s，2 H)，8.82(d，1 H)，9.20(s，1 H)，9.53(s，1 H)。 TLC: Rf 0.54 (hexane: ethyl acetate = 1: 2); 1 H -NMR (DMSO-d 6): δ 2.11-2.24 (m, 2 H), 2.64 (t, 2 H), 4.05 (t , 2 H), 7.24 (d, 2 H), 7.68 (d, 2 H), 7.90 (s, 1 H), 8.39 (s, 1 H), 8.57 (s, 1 H), 8.73 (s, 2) H), 8.82 (d, 1 H), 9.20 (s, 1 H), 9.53 (s, 1 H).

實施例85-9：1-[3-羥基-5-(三氟甲基)苯基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 85-9: 1-[3-Hydroxy-5-(trifluoromethyl)phenyl]-3-(2-{4-[2-(2-o-oxy-1-pyrrolidinyl)- 1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.79(乙酸乙酯：甲醇=10：1)；1H-NMR(DMSO-d6)：δ 2.16(quint，2 H)，2.64(t，2 H)，4.05(t，2 H)，6.65(s，1 H)，7.16-7.31(m，4 H)，7.62-7.71(m，2 H)，7.90(s，1 H)，8.71(s，2 H)，8.89(s，1 H)，9.20(s，1 H)，10.1(s，1 H)。 TLC: Rf 0.79 (ethyl acetate: methanol = 10: 1); 1 H -NMR (DMSO-d 6): δ 2.16 (quint, 2 H), 2.64 (t, 2 H), 4.05 (t, 2 H ), 6.65 (s, 1 H), 7.16-7.31 (m, 4 H), 7.62-7.71 (m, 2 H), 7.90 (s, 1 H), 8.71 (s, 2 H), 8.89 (s, 1 H), 9.20 (s, 1 H), 10.1 (s, 1 H).

實施例85-10：1-[2-環丙基-5-(三氟甲基)-3-吡啶基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 85-10: 1-[2-Cyclopropyl-5-(trifluoromethyl)-3-pyridyl]-3-(2-{4-[2-(2-Sideoxy-1-) Pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.43(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 1.08(t，4 H)，2.12-2.23(m，2 H)，2.27-2.30(m，1 H)，2.64(t，2 H)，4.05(t，2 H)，7.24(d，2 H)，7.68(d，2 H)，7.90(s，1 H)，8.48(d，2 H)，8.74(s，2 H)，8.91(s，1 H)，9.37(s，1 H)。 TLC: Rf 0.43 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 1.08 (t, 4 H), 2.12 - 2.23 (m, 2 H), 2.27 - 2.30 (m, 1 H), 2.64 (t, 2 H), 4.05 (t, 2 H), 7.24 (d, 2 H), 7.68 (d, 2 H), 7.90 (s, 1 H), 8.48 (d, 2 H), 8.74 ( s, 2 H), 8.91 (s, 1 H), 9.37 (s, 1 H).

實施例85-11：1-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[4-(三氟甲基)-2-吡啶基]脲 Example 85-11: 1-(2-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl )-3-[4-(trifluoromethyl)-2-pyridyl]urea

TLC：Rf 0.42(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 2.11-2.24(m，2 H)，2.64(t，2 H)，4.05(t，2 H)，7.24(d，2 H)，7.39(dd，1 H)，7.68(d，2 H)，7.90(s，1 H)，7.99(s，1 H)，8.54(d，1 H)，8.78(s，2 H)，9.90(s，1 H)，9.94(s，1 H)。 TLC: Rf 0.42 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 2.11-2.24 (m, 2 H), 2.64 (t, 2 H), 4.05 (t, 2 H), 7.24 ( d, 2 H), 7.39 (dd, 1 H), 7.68 (d, 2 H), 7.90 (s, 1 H), 7.99 (s, 1 H), 8.54 (d, 1 H), 8.78 (s, 2 H), 9.90 (s, 1 H), 9.94 (s, 1 H).

實施例85-12：1-[2-(1-氧負離子基-3-吡啶基)-5-(三氟甲基)-3-吡啶基]-3-(6-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)脲 Example 85-12: 1-[2-(1-Oxo-n-yl-3-pyridyl)-5-(trifluoromethyl)-3-pyridyl]-3-(6-{4-[2- (2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-3-pyridyl)urea

TLC：Rf 0.32(乙酸乙酯：甲醇：氨水=9：1：0.5)；1H-NMR(DMSO-d6)：δ 2.10-2.20(m，2 H)，2.64(t，2 H)，4.04(t，2 H)，7.05(d，1 H)，7.12(d，2 H)，7.57-7.66(m，4 H)，7.87(s，1 H)，8.00(dd，1 H)，8.13(d，1 H)，8.35-8.37(m，1 H)，8.48(s，2 H)，8.74(s，1 H)，8.80(s，1 H)，9.27(s，1 H)。 TLC: Rf 0.32 (ethyl acetate:methanol:methanol = 9:1:0.5); 1 H-NMR (DMSO-d 6 ): δ 2.10-2.20 (m, 2 H), 2.64 (t, 2 H), 4.04 (t, 2 H), 7.05 (d, 1 H), 7.12 (d, 2 H), 7.57-7.66 (m, 4 H), 7.87 (s, 1 H), 8.00 (dd, 1 H), 8.13 (d, 1 H), 8.35-8.37 (m, 1 H), 8.48 (s, 2 H), 8.74 (s, 1 H), 8.80 (s, 1 H), 9.27 (s, 1 H).

實施例85-13：1-[2-(1-氧負離子基-3-吡啶基)-5-(三氟甲基)-3-吡啶基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 85-13: 1-[2-(1-Oxo-n-yl-3-pyridyl)-5-(trifluoromethyl)-3-pyridyl]-3-(2-{4-[2- (2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.18(乙酸乙酯：甲醇：氨水=9：1：0.5)；1H-NMR(DMSO-d6)：δ 2.10-2.25(m，2 H)，2.64(t，2 H)，4.05(t，2 H)，7.22(d，2 H)，7.57-7.60(m，2 H)，7.67(d，2 H)，7.90(s，1 H)，8.34-8.37(m，1 H)，8.48(s，1 H)，8.62(s，1 H)，8.68(s，2 H)，8.77-8.78(m，2 H)，9.34(s，1 H)。 TLC: Rf 0.18 (ethyl acetate:methanol:methanol = 9:1: 0.5); 1 H-NMR (DMSO-d 6 ): δ 2.10-2.25 (m, 2 H), 2.64 (t, 2 H), 4.05 (t, 2 H), 7.22 (d, 2 H), 7.57-7.60 (m, 2 H), 7.67 (d, 2 H), 7.90 (s, 1 H), 8.34 - 8.37 (m, 1 H) ), 8.48 (s, 1 H), 8.62 (s, 1 H), 8.68 (s, 2 H), 8.77-8.78 (m, 2 H), 9.34 (s, 1 H).

實施例85-14：1-(6-{2-氟-4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)-3-[2-苯基-5-(三氟甲基)-3-吡啶基]脲 Example 85-14: 1-(6-{2-Fluoro-4-[2-(2-o-oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}- 3-pyridyl)-3-[2-phenyl-5-(trifluoromethyl)-3-pyridyl]urea

TLC：Rf 0.50(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 2.11-2.23(m，2 H)，2.64(t，2 H)，4.05(t，2 H)，7.11(d，1 H)，7.31(t，1 H)，7.45(dd，1 H)，7.53-7.60(m，3 H)，7.64(dd，1 H)，7.70(dd，2 H)，7.98(s，1 H)，8.02-8.08(m，2 H)，8.29(s，1 H)，8.70(s，1 H)，8.78(s，1 H)，9.38(s，1 H)。 TLC: Rf 0.50 (ethyl acetate); 1 H-NMR (DMSO -d 6): δ 2.11-2.23 (m, 2 H), 2.64 (t, 2 H), 4.05 (t, 2 H), 7.11 ( d,1 H), 7.31 (t, 1 H), 7.45 (dd, 1 H), 7.53-7.60 (m, 3 H), 7.64 (dd, 1 H), 7.70 (dd, 2 H), 7.98 ( s, 1 H), 8.02-8.08 (m, 2 H), 8.29 (s, 1 H), 8.70 (s, 1 H), 8.78 (s, 1 H), 9.38 (s, 1 H).

實施例85-15：1-(6-{2-氟-4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)-3-[2-(3-吡啶基)-5-(三氟甲基)苯基]脲 Example 85-15: 1-(6-{2-Fluoro-4-[2-(2-o-oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}- 3-pyridyl)-3-[2-(3-pyridyl)-5-(trifluoromethyl)phenyl]urea

TLC：Rf 0.46(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 2.11-2.22(m，2 H)，2.64(t，2 H)，4.05(t，2 H)，7.10(d，1 H)，7.30(t，1 H)，7.46(dd，1 H)，7.48(s，2 H)，7.56(dd，1 H)，7.71(dd，1 H)，7.88(dt，1 H)，7.98(d，2 H)，8.02(d，1 H)，8.09(s，1 H)，8.42(s，1 H)，8.64(d，1 H)，8.68(d，1 H)，9.15(s，1 H)。 TLC: Rf 0.46 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 2.11-2.22 (m, 2 H), 2.64 (t, 2 H), 4.05 (t, 2 H), 7.10 ( d, 1 H), 7.30 (t, 1 H), 7.46 (dd, 1 H), 7.48 (s, 2 H), 7.56 (dd, 1 H), 7.71 (dd, 1 H), 7.88 (dt, 1 H), 7.98 (d, 2 H), 8.02 (d, 1 H), 8.09 (s, 1 H), 8.42 (s, 1 H), 8.64 (d, 1 H), 8.68 (d, 1 H) ), 9.15 (s, 1 H).

實施例85-16：1-[2-(4-{2-[2-(2-羥基-2-丙基)-1-吡咯啶基]-1，3-噻唑-5-基}苯氧基)-5-嘧啶基]-3-[2-苯基-5-(三氟甲基)-3- 吡啶基]脲 Example 85-16: 1-[2-(4-{2-[2-(2-hydroxy-2-propyl)-1-pyrrolidinyl]-1,3-thiazol-5-yl}phenoxy 5-)-5-pyrimidinyl]-3-[2-phenyl-5-(trifluoromethyl)-3- Pyridyl]urea

TLC：Rf 0.35(氯仿：甲醇=19：1)；1H-NMR(DMSO-d6)：δ 0.94(s，6 H)，1.56-1.72(m，1 H)，1.83-2.16(m，3 H)，3.35-3.54(m，2 H)，3.65(t，1 H)，7.09-7.15(m，2 H)，7.21(s，1 H)，7.35-7.50(m，5 H)，7.58-7.64(m，3 H)，8.61-8.68(m，4 H)，8.86(d，1 H)，8.90(s，1 H)。 TLC: Rf 0.35 (chloroform:methanol = 19:1); 1 H-NMR (DMSO-d 6 ): δ 0.94 (s, 6 H), 1.56-1.72 (m, 1 H), 1.83-2.16 (m, 3 H), 3.35-3.54 (m, 2 H), 3.65 (t, 1 H), 7.09-7.15 (m, 2 H), 7.21 (s, 1 H), 7.35-7.50 (m, 5 H), 7.58-7.64 (m, 3 H), 8.61 - 8.68 (m, 4 H), 8.86 (d, 1 H), 8.90 (s, 1 H).

實施例85-17：1-[2-(2-甲基-4-吡啶基)-5-(三氟甲基)苯基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 85-17: 1-[2-(2-Methyl-4-pyridyl)-5-(trifluoromethyl)phenyl]-3-(2-{4-[2-(2- side) Oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.47(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 2.11-2.22(m，2 H)，2.54(s，3 H)，2.64(t，2 H)，4.05(t，2 H)，7.22(d，2 H)，7.27(d，1 H)，7.35(s，1 H)，7.44-7.52(m，2 H)，7.67(d，2 H)，7.89(s，1 H)，8.17(s，1 H)，8.42(s，1 H)，8.59(d，1 H)，8.65(s，2 H)，9.29(s，1 H)。 TLC: Rf 0.47 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 2.11-2.22 (m, 2 H), 2.54 (s, 3 H), 2.64 (t, 2 H), 4.05 ( t, 2 H), 7.22 (d, 2 H), 7.27 (d, 1 H), 7.35 (s, 1 H), 7.44-7.52 (m, 2 H), 7.67 (d, 2 H), 7.89 ( s, 1 H), 8.17 (s, 1 H), 8.42 (s, 1 H), 8.59 (d, 1 H), 8.65 (s, 2 H), 9.29 (s, 1 H).

實施例85-18：1-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-(4-哌啶基)-5-(三氟甲基)苯基]脲 Example 85-18: 1-(2-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl )-3-[2-(4-piperidinyl)-5-(trifluoromethyl)phenyl]urea

TLC：Rf 0.19(乙酸乙酯：甲醇：氨水=9：1：0.5)；1H-NMR(DMSO-d6)：δ 1.40-1.70(m，4 H)，2.10-2.20(m，2 H)，2.61-2.75(m，4 H)，2.85-3.10(m，3 H)，4.05(t，2 H)，7.22(d，2 H)，7.39-7.48(m，2 H)，7.67(d，2 H)，7.89(s，1 H)，8.05(s，1 H)，8.55(s，1 H)，8.73(s，2 H)，9.40(s，1 H)。 TLC: Rf 0.19 (ethyl acetate:methanol:methanol = 9:1:0.5); 1 H-NMR (DMSO-d 6 ): δ 1.40-1.70 (m, 4 H), 2.10-2.20 (m, 2 H) ), 2.61-2.75 (m, 4 H), 2.85-3.10 (m, 3 H), 4.05 (t, 2 H), 7.22 (d, 2 H), 7.39-7.48 (m, 2 H), 7.67 ( d, 2 H), 7.89 (s, 1 H), 8.05 (s, 1 H), 8.55 (s, 1 H), 8.73 (s, 2 H), 9.40 (s, 1 H).

實施例85-19：1-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-(1，2，3，6-四氫-4-吡啶基)-5-(三氟甲基)苯基]脲 Example 85-19: 1-(2-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl )-3-[2-(1,2,3,6-tetrahydro-4-pyridyl)-5-(trifluoromethyl)phenyl]urea

TLC：Rf 0.29(乙酸乙酯：甲醇：氨水=9：1：0.5)；1H-NMR(DMSO-d6)：δ 2.14-2.20(m，4 H)，2.64(t，2 H)，2.94-2.99(m，2 H)，3.38(s，2 H)，4.05(t，2 H)，5.83(s，1 H)，7.22(d，2 H)，7.25-7.40(m，2 H)，7.67(d，2 H)，7.89(s，1 H)，8.09(s，1 H)，8.30(s，1 H)，8.71(s，2 H)，9.60(s，1 H)。 TLC: Rf 0.29 (ethyl acetate:methanol:methanol = 9:1: 0.5); 1 H-NMR (DMSO-d 6 ): δ 2.14-2.20 (m, 4 H), 2.64 (t, 2 H), 2.94-2.99 (m, 2 H), 3.38 (s, 2 H), 4.05 (t, 2 H), 5.83 (s, 1 H), 7.22 (d, 2 H), 7.25-7.40 (m, 2 H) ), 7.67 (d, 2 H), 7.89 (s, 1 H), 8.09 (s, 1 H), 8.30 (s, 1 H), 8.71 (s, 2 H), 9.60 (s, 1 H).

實施例85-20：1-(4-甲基-6-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)-3-[2-苯基-5-(三氟甲基)-3-吡啶基]脲 Example 85-20: 1-(4-Methyl-6-{4-[2-(2-o-oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy} -3-pyridyl)-3-[2-phenyl-5-(trifluoromethyl)-3-pyridyl]urea

TLC：Rf 0.51(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 2.10-2.23(m，5 H)，2.64(t，2 H)，4.05(t，2 H)，6.96(s，1 H)，7.11(d，2 H)，7.52-7.57(m，3 H)，7.66(d，3 H)，7.69(dd，1 H)，7.86(s，1 H)，8.24(s，1 H)，8.52(s，1 H)，8.59 (s，1 H)，8.69(s，2 H)。 TLC: Rf 0.51 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 2.10-2.23 (m, 5 H), 2.64 (t, 2 H), 4.05 (t, 2 H), 6.96 ( s, 1 H), 7.11 (d, 2 H), 7.52-7.57 (m, 3 H), 7.66 (d, 3 H), 7.69 (dd, 1 H), 7.86 (s, 1 H), 8.24 ( s, 1 H), 8.52 (s, 1 H), 8.59 (s, 1 H), 8.69 (s, 2 H).

實施例85-21：1-(4-甲基-6-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)-3-[2-(3-吡啶基)-5-(三氟甲基)苯基]脲 Example 85-21:1-(4-Methyl-6-{4-[2-(2-o-oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy} -3-pyridyl)-3-[2-(3-pyridyl)-5-(trifluoromethyl)phenyl]urea

TLC：Rf 0.46(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 2.10-2.24(m，2 H)，2.17(s，3 H)，2.64(t，2 H)，4.05(t，2 H)，6.94(s，1 H)，7.11(d，2 H)，7.49(s，2 H)，7.56(dd，1 H)，7.64(d，2 H)，7.86(s，1 H)，7.90(dd，1 H)，8.19(s，1 H)，8.30(d，2 H)，8.37(s，1 H)，8.67(d，2 H)。 TLC: Rf 0.46 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 2.10-2.24 (m, 2 H), 2.17 (s, 3 H), 2.64 (t, 2 H), 4.05 ( t,2 H), 6.94 (s, 1 H), 7.11 (d, 2 H), 7.49 (s, 2 H), 7.56 (dd, 1 H), 7.64 (d, 2 H), 7.86 (s, 1 H), 7.90 (dd, 1 H), 8.19 (s, 1 H), 8.30 (d, 2 H), 8.37 (s, 1 H), 8.67 (d, 2 H).

實施例85-22：1-[2-(1-甲基-4-哌啶基)-5-(三氟甲基)苯基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 85-22: 1-[2-(1-Methyl-4-piperidinyl)-5-(trifluoromethyl)phenyl]-3-(2-{4-[2-(2- Oxo-l-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.21(乙酸乙酯：甲醇：氨水=9：1：0.5)；1H-NMR(DMSO-d6)：δ 1.60-1.80(m，4 H)，1.98-2.20(m，7 H)，2.60-2.90(m，5 H)，4.05(t，2 H)，7.23(d，2 H)，7.41(d，1 H)，7.50(d，1 H)，7.68(d，2 H)，7.90(s，1 H)，8.05(s，1 H)，8.44(s，1 H)，8.73(s，2 H)，9.28(s，1 H)。 TLC: Rf 0.21 (ethyl acetate:methanol:methanol = 9:1:0.5); 1 H-NMR (DMSO-d 6 ): δ 1.60-1.80 (m, 4 H), 1.98-2.20 (m, 7 H) ), 2.60-2.90 (m, 5 H), 4.05 (t, 2 H), 7.23 (d, 2 H), 7.41 (d, 1 H), 7.50 (d, 1 H), 7.68 (d, 2 H) ), 7.90 (s, 1 H), 8.05 (s, 1 H), 8.44 (s, 1 H), 8.73 (s, 2 H), 9.28 (s, 1 H).

實施例85-23：1-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-(1H-吡唑-3-基)-5-(三氟甲基)苯基]脲 Example 85-23: 1-(2-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl )-3-[2-(1H-pyrazol-3-yl)-5-(trifluoromethyl)phenyl]urea

TLC：Rf 0.19(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 2.23-2.32(m，2 H)，2.71(s，2 H)，4.18(t，2 H)，5.95(d，1 H)，7.16(d，2 H)，7.26(s，2 H)，7.40(d，2 H)，7.52-7.60(m，3 H)，7.89(s，1 H)，8.55(s，2 H)，8.85(s，1 H)，9.29(d，1 H)。 TLC: Rf 0.19 (ethyl acetate); 1 H-NMR (DMSO -d 6): δ 2.23-2.32 (m, 2 H), 2.71 (s, 2 H), 4.18 (t, 2 H), 5.95 ( d, 1 H), 7.16 (d, 2 H), 7.26 (s, 2 H), 7.40 (d, 2 H), 7.52-7.60 (m, 3 H), 7.89 (s, 1 H), 8.55 ( s, 2 H), 8.85 (s, 1 H), 9.29 (d, 1 H).

實施例85-24：1-(2-甲基-6-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)-3-[2-(3-吡啶基)-5-(三氟甲基)苯基]脲 Example 85-24: 1-(2-Methyl-6-{4-[2-(2-o-oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy} -3-pyridyl)-3-[2-(3-pyridyl)-5-(trifluoromethyl)phenyl]urea

TLC：Rf 0.35(乙酸乙酯：甲醇=19：1)；1H-NMR(DMSO-d6)：δ 2.13-2.22(m，5 H)，2.63(t，2 H)，4.04(t，2 H)，6.84(d，1 H)，7.10(d，2 H)，7.49(s，2 H)，7.57(dd，1 H)，7.62(d，2 H)，7.86(s，1 H)，7.89-7.93(m，1 H)，8.01(d，1 H)，8.32(s，1 H)，8.34(s，1 H)，8.41(s，1 H)，8.66-8.68(m，2 H)。 TLC: Rf 0.35 (ethyl acetate: methanol = 19: 1); 1 H -NMR (DMSO-d 6): δ 2.13-2.22 (m, 5 H), 2.63 (t, 2 H), 4.04 (t, 2 H), 6.84 (d, 1 H), 7.10 (d, 2 H), 7.49 (s, 2 H), 7.57 (dd, 1 H), 7.62 (d, 2 H), 7.86 (s, 1 H) ), 7.89-7.93 (m, 1 H), 8.01 (d, 1 H), 8.32 (s, 1 H), 8.34 (s, 1 H), 8.41 (s, 1 H), 8.66-8.68 (m, 2 H).

實施例85-25：1-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[3-(三氟甲基)環己基]脲 Example 85-25: 1-(2-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl )-3-[3-(trifluoromethyl)cyclohexyl]urea

TLC：Rf 0.41(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 1.08-2.05(m，9 H)，2.16(m，2 H)，2.64(t，2 H)，3.55(m，1 H)，4.05(t，2 H)，6.43(d，1 H)，7.19(d，2 H)，7.65(d，2 H)，7.88(s，1 H)，8.56(s，1 H)，8.62(s，2 H)。 TLC: Rf 0.41 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 1.08-2.05 (m, 9 H), 2.16 (m, 2 H), 2.64 (t, 2 H), 3.55 ( m,1 H), 4.05 (t, 2 H), 6.43 (d, 1 H), 7.19 (d, 2 H), 7.65 (d, 2 H), 7.88 (s, 1 H), 8.56 (s, 1 H), 8.62 (s, 2 H).

實施例85-26：2-{[(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)胺基甲醯基]胺基}-4-(三氟甲基)苯甲酸 Examples 85-26: 2-{[(2-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5- Pyrimidinyl)aminomethylindenyl]amino}-4-(trifluoromethyl)benzoic acid

TLC：Rf 0.48(乙酸乙酯：甲醇：乙酸=9：1：0.1)；1H-NMR(DMSO-d6)：δ 2.11-2.23(m，2 H)，2.64(t，2 H)，4.05(t，2 H)，7.23(d，2 H)，7.40(d，1 H)，7.67(d，2 H)，7.89(s，1 H)，8.14(d，1 H)，8.73(s，2 H)，8.80(s，1 H)，10.3(s，1 H)，10.7(s，1 H)，14.1(s，1 H)。 TLC: Rf 0.48 (ethyl acetate: methanol: acetic acid = 9: 1: 0.1); 1 H-NMR (DMSO-d 6): δ 2.11-2.23 (m, 2 H), 2.64 (t, 2 H), 4.05 (t, 2 H), 7.23 (d, 2 H), 7.40 (d, 1 H), 7.67 (d, 2 H), 7.89 (s, 1 H), 8.14 (d, 1 H), 8.73 ( s, 2 H), 8.80 (s, 1 H), 10.3 (s, 1 H), 10.7 (s, 1 H), 14.1 (s, 1 H).

實施例85-27：1-[2-(2-羥基-2-丙基)-5-(三氟甲基)苯基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Examples 85-27: 1-[2-(2-Hydroxy-2-propyl)-5-(trifluoromethyl)phenyl]-3-(2-{4-[2-(2-sided oxygen) -ylpyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.54(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 1.57(s，6 H)，2.10-2.23(m，2 H)，2.64(t，2 H)，4.05(t，2 H)，6.21(s，1 H)，7.22(d，2 H)，7.29(d，1 H)，7.47(d，1 H)，7.67(d，2 H)，7.89(s，1 H)，8.36(s，1 H)，8.73(s，2 H)，9.88(s，1 H)，10.0(s，1 H)。 TLC: Rf 0.54 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 1.57 (s, 6 H), 2.10-2.23 (m, 2 H), 2.64 (t, 2 H), 4.05 ( t,2 H), 6.21 (s, 1 H), 7.22 (d, 2 H), 7.29 (d, 1 H), 7.47 (d, 1 H), 7.67 (d, 2 H), 7.89 (s, 1 H), 8.36 (s, 1 H), 8.73 (s, 2 H), 9.88 (s, 1 H), 10.0 (s, 1 H).

實施例85-28：1-(2-甲基-6-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)-3-[2-苯基-5-(三氟甲基)-3-吡啶基]脲 Example 85-28: 1-(2-Methyl-6-{4-[2-(2-o-oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy} -3-pyridyl)-3-[2-phenyl-5-(trifluoromethyl)-3-pyridyl]urea

TLC：Rf 0.70(乙酸乙酯：甲醇=19：1)；1H-NMR(DMSO-d6)：δ 2.10-2.25(m，5 H)，2.64(t，2 H)，4.05(t，2 H)，6.86(d，1 H)，7.11(d，2 H)，7.55-7.71(m，7 H)，7.87(s，1 H)，8.06(d，1 H)，8.57(s，1 H)，8.63(s，1 H)，8.71(s，2 H)。 TLC: Rf 0.70 (ethyl acetate: methanol = 19: 1); 1 H -NMR (DMSO-d 6): δ 2.10-2.25 (m, 5 H), 2.64 (t, 2 H), 4.05 (t, 2 H), 6.86 (d, 1 H), 7.11 (d, 2 H), 7.55-7.71 (m, 7 H), 7.87 (s, 1 H), 8.06 (d, 1 H), 8.57 (s, 1 H), 8.63 (s, 1 H), 8.71 (s, 2 H).

實施例85-29：1-[2-(1H-咪唑-1-基)-5-(三氟甲基)苯基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 85-29: 1-[2-(1H-Imidazol-1-yl)-5-(trifluoromethyl)phenyl]-3-(2-{4-[2-(2-trioxy) -1-pyrrolidyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.34(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 2.10-2.23(m，2 H)，2.64(t，2 H)，4.05(t，2 H)，7.19(d，2 H)，7.23(s，1 H)，7.49(s，1 H)，7.54(s，2 H)，7.67(d，2 H)，7.90(s，1 H)，7.97(s，1 H)，8.32(s，1 H)，8.50(s，1 H)，8.66(s，2 H)，9.42(s，1 H)。 TLC: Rf 0.34 (ethyl acetate); 1 H-NMR (DMSO -d 6): δ 2.10-2.23 (m, 2 H), 2.64 (t, 2 H), 4.05 (t, 2 H), 7.19 ( d, 2 H), 7.23 (s, 1 H), 7.49 (s, 1 H), 7.54 (s, 2 H), 7.67 (d, 2 H), 7.90 (s, 1 H), 7.97 (s, 1 H), 8.32 (s, 1 H), 8.50 (s, 1 H), 8.66 (s, 2 H), 9.42 (s, 1 H).

實施例85-30：1-[3，5-雙(三氟甲基)苯基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 85-30: 1-[3,5-Bis(Trifluoromethyl)phenyl]-3-(2-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1 , 3-thiazole-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.54(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 2.10-2.22(m，2 H)，2.64(t，2 H)，4.05(t，2 H)，7.24(d，2 H)，7.62-7.72(m，3 H)，7.90(s，1 H)，8.14(s，2 H)，8.72(s，2 H)，9.20(s，1 H)，9.66(s，1 H)。 TLC: Rf 0.54 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 2.10 - 2.22 (m, 2 H), 2.64 (t, 2 H), 4.05 (t, 2 H), 7.24 ( d, 2 H), 7.62-7.72 (m, 3 H), 7.90 (s, 1 H), 8.14 (s, 2 H), 8.72 (s, 2 H), 9.20 (s, 1 H), 9.66 ( s, 1 H).

實施例85-31：1-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-苯基-5-(三氟甲基)環己基]脲 Example 85-31:1-(2-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl )-3-[2-phenyl-5-(trifluoromethyl)cyclohexyl]urea

TLC：Rf 0.62(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 1.34-1.87(m，8 H)，2.10-2.25(m，2 H)，2.64(t，2 H)，3.85-4.00(m，1 H)，4.05(t，2 H)，6.22(d，1 H)，7.11-7.20(m，3 H)，7.22-7.34(m，4 H)，7.64(d，2 H)，7.88(s，1 H)，8.45 (s，1 H)，8.51(s，2 H)。 TLC: Rf 0.62 (ethyl acetate); 1 H-NMR (DMSO -d 6): δ 1.34-1.87 (m, 8 H), 2.10-2.25 (m, 2 H), 2.64 (t, 2 H), 3.85-4.00 (m, 1 H), 4.05 (t, 2 H), 6.22 (d, 1 H), 7.11-7.20 (m, 3 H), 7.22-7.34 (m, 4 H), 7.64 (d, 2 H), 7.88 (s, 1 H), 8.45 (s, 1 H), 8.51 (s, 2 H).

實施例85-32：1-(2-{4-[2-(2-甲基-5-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-苯基-5-(三氟甲基)-3-吡啶基]脲 Example 85-32: 1-(2-{4-[2-(2-methyl-5-o-oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy} -5-pyrimidinyl)-3-[2-phenyl-5-(trifluoromethyl)-3-pyridyl]urea

TLC：Rf 0.54(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 1.41(d，3 H)，1.77-1.88(m，1 H)，2.29-2.58(m，2 H)，2.81-2.90(m，1 H)，4.60-4.71(m，1 H)，7.22(d，2 H)，7.52-7.60(m，3 H)，7.63-7.70(m，4 H)，7.90(s，1 H)，8.43(s，1 H)，8.67(s，2 H)，8.71-8.78(m，2 H)，9.47(s，1 H)。 TLC: Rf 0.54 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 1.41 (d, 3 H), 1.77-1.88 (m, 1 H), 2.29-2.58 (m, 2 H), 2.81-2.90 (m, 1 H), 4.60-4.71 (m, 1 H), 7.22 (d, 2 H), 7.52-7.60 (m, 3 H), 7.63-7.70 (m, 4 H), 7.90 ( s, 1 H), 8.43 (s, 1 H), 8.67 (s, 2 H), 8.71 - 8.78 (m, 2 H), 9.47 (s, 1 H).

實施例85-33：1-(2-{4-[2-(2-甲基-5-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-(3-吡啶基)-5-(三氟甲基)苯基]脲 Example 85-33: 1-(2-{4-[2-(2-methyl-5-o-oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy} -5-pyrimidinyl)-3-[2-(3-pyridyl)-5-(trifluoromethyl)phenyl]urea

TLC：Rf 0.14(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 1.42(d，3 H)，1.76-1.91(m，1 H)，2.32-2.58(m，2 H)，2.78-2.93(m，1 H)，4.60-4.70(m，1 H)，7.19-7.25(m，2 H)，7.47-7.58(m，3 H)，7.64-7.69(m，2 H)，7.86-7.92(m，2 H)，8.24(s，1 H)，8.38(s，1 H)，8.62-8.72(m，4 H)，9.25(s，1 H)。 TLC: Rf 0.14 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 1.42 (d, 3 H), 1.76-1.91 (m, 1 H), 2.32 - 2.58 (m, 2 H), 2.78-2.93 (m, 1 H), 4.60-4.70 (m, 1 H), 7.19-7.25 (m, 2 H), 7.47-7.58 (m, 3 H), 7.64-7.69 (m, 2 H), 7.86-7.92 (m, 2 H), 8.24 (s, 1 H), 8.38 (s, 1 H), 8.62 - 8.72 (m, 4 H), 9.25 (s, 1 H).

實施例85-34：1-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-(3-吡啶基)-5-(三氟甲基)環己基]脲 Example 85-34: 1-(2-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl )-3-[2-(3-pyridyl)-5-(trifluoromethyl)cyclohexyl]urea

TLC：Rf 0.74(乙酸乙酯)； 1H-NMR(DMSO-d6)：δ 1.38-2.21(m，8 H)，2.11-2.24(m，2 H)，2.64(t，2 H)，3.92-4.03(m，1 H)，4.05(t，2 H)，6.34(d，1 H)，7.17(d，2 H)，7.30(dd，1 H)，7.58-7.70(m，3 H)，7.89(s，1 H)，8.37(dd，1 H)，8.45(s，2 H)，8.50(s，2 H)。 TLC: Rf 0.74 (ethyl acetate); 1 H-NMR (DMSO -d 6): δ 1.38-2.21 (m, 8 H), 2.11-2.24 (m, 2 H), 2.64 (t, 2 H), 3.92-4.03 (m, 1 H), 4.05 (t, 2 H), 6.34 (d, 1 H), 7.17 (d, 2 H), 7.30 (dd, 1 H), 7.58-7.70 (m, 3 H) ), 7.89 (s, 1 H), 8.37 (dd, 1 H), 8.45 (s, 2 H), 8.50 (s, 2 H).

實施例85-35：1-[5-(2-甲基-2-丙基)-2-(3-吡啶基)苯基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 85-35: 1-[5-(2-Methyl-2-propyl)-2-(3-pyridyl)phenyl]-3-(2-{4-[2-(2- side) Oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.27(乙酸乙酯：甲醇=9：1)；1H-NMR(DMSO-d6)：δ 1.31(s，9 H)，2.11-2.21(m，2 H)，2.66(t，2 H)，4.05(t，2 H)，7.19-7.28(m，4 H)，7.48(dd，1 H)，7.66(d，2 H)，7.79-7.85(m，2 H)，7.89(s，1 H)，8.06(s，1 H)，8.56-8.60(m，4 H)，9.03(s，1 H)。 TLC: Rf 0.27 (ethyl acetate:methanol = 9:1); 1 H-NMR (DMSO-d 6 ): δ 1.31 (s, 9 H), 2.11-2.21 (m, 2 H), 2.66 (t, 2 H), 4.05 (t, 2 H), 7.19-7.28 (m, 4 H), 7.48 (dd, 1 H), 7.66 (d, 2 H), 7.79-7.85 (m, 2 H), 7.89 ( s, 1 H), 8.06 (s, 1 H), 8.56-8.60 (m, 4 H), 9.03 (s, 1 H).

實施例85-36：1-(5-甲基-6-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)-3-[2-苯基-5-(三氟甲基)-3-吡啶基]脲 Example 85-36: 1-(5-Methyl-6-{4-[2-(2-o-oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy} -3-pyridyl)-3-[2-phenyl-5-(trifluoromethyl)-3-pyridyl]urea

TLC：Rf 0.61(乙酸乙酯：甲醇=9：1)；1H-NMR(DMSO-d6)：δ 2.10-2.28(m，5 H)，2.63(t，2 H)，4.04(t，2 H)，7.07(d，2 H)，7.54-7.66(m，7 H)，7.85-7.93(m，3 H)，8.27(s，1 H)，8.69(s，1 H)，8.79(s，1 H)，9.39(s，1 H)。 TLC: Rf 0.61 (ethyl acetate: methanol = 9: 1); 1 H -NMR (DMSO-d 6): δ 2.10-2.28 (m, 5 H), 2.63 (t, 2 H), 4.04 (t, 2 H), 7.07 (d, 2 H), 7.54-7.66 (m, 7 H), 7.85-7.93 (m, 3 H), 8.27 (s, 1 H), 8.69 (s, 1 H), 8.79 ( s, 1 H), 9.39 (s, 1 H).

實施例85-37：1-(5-甲基-6-{4-[2-(2-側氧基-1-吡咯啶基)-1， 3-噻唑-5-基]苯氧基}-3-吡啶基)-3-[2-(3-吡啶基)-5-(三氟甲基)苯基]脲 Example 85-37: 1-(5-Methyl-6-{4-[2-(2-o-oxy-1-pyrrolidinyl)-1, 3-thiazol-5-yl]phenoxy}-3-pyridyl)-3-[2-(3-pyridyl)-5-(trifluoromethyl)phenyl]urea

TLC：Rf 0.56(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 2.10-2.27(m，5 H)，2.63(t，2 H)，4.04(t，2 H)，7.06(d，2 H)，7.47-7.62(m，5 H)，7.84-7.93(m，4 H)，8.07(s，1 H)，8.43(s，1 H)，8.63-8.68(m，2 H)，9.11(s，1 H)。 TLC: Rf 0.56 (ethyl acetate); 1 H-NMR (DMSO -d 6): δ 2.10-2.27 (m, 5 H), 2.63 (t, 2 H), 4.04 (t, 2 H), 7.06 ( d,2 H), 7.47-7.62 (m, 5 H), 7.84-7.93 (m, 4 H), 8.07 (s, 1 H), 8.43 (s, 1 H), 8.63-8.68 (m, 2 H) ), 9.11 (s, 1 H).

實施例85-38：1-[2-(1-甲基-6-側氧基-1，6-二氫-3-吡啶基)-5-(三氟甲基)苯基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 85-38: 1-[2-(1-Methyl-6-oxooxy-1,6-dihydro-3-pyridyl)-5-(trifluoromethyl)phenyl]-3- (2-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.65(乙酸乙酯：甲醇=9：1)；1H-NMR(DMSO-d6)：δ 2.10-2.21(m，2 H)，2.64(t，2 H)，3.49(s，3 H)，4.05(t，2 H)，6.53(d，1 H)，7.23(d，2 H)，7.44(d，2 H)，7.47(dd，1 H)，7.67(dd，2 H)，7.90(s，1 H)，7.95(d，1 H)，8.25(s，1 H)，8.43(s，1 H)，8.69(s，2 H)，9.31(s，1 H)。 TLC: Rf 0.65 (ethyl acetate: methanol = 9: 1); 1 H -NMR (DMSO-d 6): δ 2.10-2.21 (m, 2 H), 2.64 (t, 2 H), 3.49 (s, 3 H), 4.05 (t, 2 H), 6.53 (d, 1 H), 7.23 (d, 2 H), 7.44 (d, 2 H), 7.47 (dd, 1 H), 7.67 (dd, 2 H) ), 7.90 (s, 1 H), 7.95 (d, 1 H), 8.25 (s, 1 H), 8.43 (s, 1 H), 8.69 (s, 2 H), 9.31 (s, 1 H).

實施例85-39：1-(6-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)-3-[3-(三氟甲基)苯基]脲 Example 85-39: 1-(6-{4-[2-(ethylamino)-1,3-thiazol-5-yl]phenoxy}-3-pyridyl)-3-[3-( Trifluoromethyl)phenyl]urea

TLC：Rf 0.75(乙酸乙酯：甲醇=19：1)； 1H-NMR(DMSO-d6)：δ 1.16(t，3 H)，3.20-3.32(m，2 H)，6.99-7.06(m，3 H)，7.30(d，1 H)，7.39-7.59(m，5 H)，7.69(t，1 H)，7.97-8.01(m，2 H)，8.18(d，1 H)，8.88(s，1 H)，9.14(s，1 H)。 TLC: Rf 0.75 (ethyl acetate:methanol = 19:1); 1 H-NMR (DMSO-d 6 ): δ 1.16 (t, 3 H), 3.20-3.32 (m, 2 H), 6.99-7.06 ( m,3 H), 7.30 (d, 1 H), 7.39-7.59 (m, 5 H), 7.69 (t, 1 H), 7.97-8.01 (m, 2 H), 8.18 (d, 1 H), 8.88 (s, 1 H), 9.14 (s, 1 H).

實施例85-40：1-(2-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[3-(三氟甲基)苯基]脲 Example 85-40: 1-(2-{4-[2-(ethylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-[3-( Trifluoromethyl)phenyl]urea

TLC：Rf 0.48(二氯甲烷：乙酸乙酯：甲醇=8：4：1)；1H-NMR(DMSO-d6)：δ 1.17(t，3 H)，3.20-3.30(m，2 H)，7.14(d，2 H)，7.32(d，1 H)，7.42-7.55(m，4 H)，7.62(d，1 H)，7.72(t，1 H)，8.97(s，1 H)，8.70(s，2 H)，9.03(s，1 H)，9.35(s，1 H)。 TLC: Rf 0.48 (dichloromethane: ethyl acetate:methanol = 8:4:1); 1 H-NMR (DMSO-d 6 ): δ 1.17 (t, 3 H), 3.20-3.30 (m, 2 H) ), 7.14 (d, 2 H), 7.32 (d, 1 H), 7.42 - 7.55 (m, 4 H), 7.62 (d, 1 H), 7.72 (t, 1 H), 8.97 (s, 1 H) ), 8.70 (s, 2 H), 9.03 (s, 1 H), 9.35 (s, 1 H).

實施例85-41：1-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[3-(3-吡啶基氧基)-5-(三氟甲基)苯基]脲 Example 85-41:1-(2-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl )-3-[3-(3-pyridyloxy)-5-(trifluoromethyl)phenyl]urea

TLC：Rf 0.44(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 2.11-2.24(m，2 H)，2.64(t，2 H)，4.05(t，2 H)，6.99(s，1 H)，7.23(d，2 H)，7.36(s，1 H)，7.47(dd，1 H)，7.56(dt，1 H)，7.64-7.70(m，3 H)，7.90(s，1 H)，8.42-8.50(m，2 H)，8.68(s，2 H)，8.98(s，1 H)，9.43(s，1 H)。 TLC: Rf 0.44 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 2.11-2.24 (m, 2 H), 2.64 (t, 2 H), 4.05 (t, 2 H), 6.99 ( s, 1 H), 7.23 (d, 2 H), 7.36 (s, 1 H), 7.47 (dd, 1 H), 7.56 (dt, 1 H), 7.64-7.70 (m, 3 H), 7.90 ( s, 1 H), 8.42-8.50 (m, 2 H), 8.68 (s, 2 H), 8.98 (s, 1 H), 9.43 (s, 1 H).

實施例85-42：1-[2-(3-羥基-3-甲基-1-丁炔-1-基)-5-(三氟甲基)-3-吡啶基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 85-42: 1-[2-(3-Hydroxy-3-methyl-1-butyn-1-yl)-5-(trifluoromethyl)-3-pyridyl]-3-(2 -{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.45(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 1.55(s，6 H)，2.10-2.23(m，2 H)，2.64(t，2 H)，4.05(t，2 H)，5.72(s，1 H)，7.23(d，2 H)，7.67(dd，2 H)，7.90(s，1 H)，8.47(s，1 H)，8.59(d，1 H)，8.68(d，1 H)，8.74(s，2 H)，9.89(s，1 H)。 TLC: Rf 0.45 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 1.55 (s, 6 H), 2.10-2.23 (m, 2 H), 2.64 (t, 2 H), 4.05 ( t,2 H), 5.72 (s, 1 H), 7.23 (d, 2 H), 7.67 (dd, 2 H), 7.90 (s, 1 H), 8.47 (s, 1 H), 8.59 (d, 1 H), 8.68 (d, 1 H), 8.74 (s, 2 H), 9.89 (s, 1 H).

實施例85-43：1-[2-(2-羥基-2-丙基)-5-(三氟甲基)-3-吡啶基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Examples 85-43: 1-[2-(2-hydroxy-2-propyl)-5-(trifluoromethyl)-3-pyridyl]-3-(2-{4-[2-(2) -Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.54(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 1.58(s，6 H)，2.11-2.24(m，2 H)，2.64(t，2 H)，4.05(t，2 H)，6.44(s，1 H)，7.23(d，2 H)，7.68(d，2 H)，7.90(s，1 H)，8.50(d，1 H)，8.74(s，2 H)，8.78(d，1 H)，10.0(s，1 H)，10.2(s，1 H)。 TLC: Rf 0.54 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 1.58 (s, 6 H), 2.11-2.24 (m, 2 H), 2.64 (t, 2 H), 4.05 ( t,2 H), 6.44 (s, 1 H), 7.23 (d, 2 H), 7.68 (d, 2 H), 7.90 (s, 1 H), 8.50 (d, 1 H), 8.74 (s, 2 H), 8.78 (d, 1 H), 10.0 (s, 1 H), 10.2 (s, 1 H).

實施例85-44：N-乙基-N-[5-(4-{[5-({[2-苯基-5-(三氟甲基)-3-吡啶基]胺基甲醯基}胺基)-2-吡啶基]氧基}苯基)-1，3-噻唑-2-基]丙醯胺 Example 85-44: N-Ethyl-N-[5-(4-{[5-({[2-phenyl-5-(trifluoromethyl)-3-pyridinyl]aminocarbamyl) }amino)-2-pyridyl]oxy}phenyl)-1,3-thiazol-2-yl]propanamide

TLC：Rf 0.29(己烷：乙酸乙酯=1：1)；1H-NMR(DMSO-d6)：δ 1.16(t，3 H)，1.28(t，3 H)，2.75(q，2 H)，4.19(q，2 H)，7.04(d，1 H)，7.13(d，2 H)，7.53-7.67(m，7 H)，7.86(s，1 H)，8.01(dd，1 H)，8.11(d，1 H)，8.29(s，1 H)，8.70(d，1 H)，8.79(s，1 H)，9.40(s，1 H)。 TLC: Rf 0.29 (hexane: ethyl acetate = 1:1); 1 H-NMR (DMSO-d 6 ): δ 1.16 (t, 3 H), 1.28 (t, 3 H), 2.75 (q, 2) H), 4.19 (q, 2 H), 7.04 (d, 1 H), 7.13 (d, 2 H), 7.53-7.67 (m, 7 H), 7.86 (s, 1 H), 8.01 (dd, 1) H), 8.11 (d, 1 H), 8.29 (s, 1 H), 8.70 (d, 1 H), 8.79 (s, 1 H), 9.40 (s, 1 H).

實施例85-45：1-[2-(6-側氧基-1，6-二氫-3-吡啶基)-5-(三氟甲基)苯基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 85-45: 1-[2-(6-Sideoxy-1,6-dihydro-3-pyridyl)-5-(trifluoromethyl)phenyl]-3-(2-{4 -[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.23(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 2.11-2.22(m，2 H)，2.64(t，2 H)，4.05(t，2 H)，6.46(d，1 H)，7.23(d，2 H)，7.46(s，1 H)，7.48(dd，2 H)，7.67(d，2 H)，7.90(s，1 H)，8.23(s，1 H)，8.38(s，1 H)，8.69(s，2 H)，9.33(s，1 H)，11.9(s，1 H)。 TLC: Rf 0.23 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 2.11-2.22 (m, 2 H), 2.64 (t, 2 H), 4.05 (t, 2 H), 6.46 ( d,1 H), 7.23 (d, 2 H), 7.46 (s, 1 H), 7.48 (dd, 2 H), 7.67 (d, 2 H), 7.90 (s, 1 H), 8.23 (s, 1 H), 8.38 (s, 1 H), 8.69 (s, 2 H), 9.33 (s, 1 H), 11.9 (s, 1 H).

實施例85-46：1-[2-甲氧基-5-(三氟甲基)-3-吡啶基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 85-46: 1-[2-Methoxy-5-(trifluoromethyl)-3-pyridyl]-3-(2-{4-[2-(2-Sideoxy-1-) Pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.56(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 2.11-2.21(m，2 H)，2.64(t，2 H)，3.49(s，3 H)，4.06(t，2 H)，7.23(d，2 H)，7.67(dd，2 H)，7.90(s，1 H)，8.19(s，1 H)，8.66(d，1 H)，8.72(s，2 H)，8.84(s，1 H)，9.61(s， 1 H)。 TLC: Rf 0.56 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 2.11-2.21. (m, 2 H), 2.64 (t, 2 H), 3.49 (s, 3 H), 4.06 ( t,2 H), 7.23 (d, 2 H), 7.67 (dd, 2 H), 7.90 (s, 1 H), 8.19 (s, 1 H), 8.66 (d, 1 H), 8.72 (s, 2 H), 8.84 (s, 1 H), 9.61 (s, 1 H).

實施例85-47：1-[5-(3-氧雜環丁烷基)-2-苯基-3-吡啶基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 85-47: 1-[5-(3-oxetanyl)-2-phenyl-3-pyridyl]-3-(2-{4-[2-(2- oxooxy) -1-pyrrolidyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.35(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 2.13-2.24(m，2 H)，2.64(t，2 H)，4.05(t，2 H)，4.33(m，1 H)，4.65(t，2 H)，4.98(dd，2 H)，7.22(d，2 H)，7.44-7.53(m，3 H)，7.60(dd，2 H)，7.67(d，2 H)，7.89(s，1 H)，8.21(s，1 H)，8.39(d，2 H)，8.66(s，2 H)，9.31(s，1 H)。 TLC: Rf 0.35 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 2.13-2.24 (m, 2 H), 2.64 (t, 2 H), 4.05 (t, 2 H), 4.33 ( m,1 H), 4.65 (t, 2 H), 4.98 (dd, 2 H), 7.22 (d, 2 H), 7.44-7.53 (m, 3 H), 7.60 (dd, 2 H), 7.67 ( d, 2 H), 7.89 (s, 1 H), 8.21 (s, 1 H), 8.39 (d, 2 H), 8.66 (s, 2 H), 9.31 (s, 1 H).

實施例85-48：1-(2-{4-[2-(2-側氧基-1-氮雜環丁烷基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-(3-吡啶基)-5-(三氟甲基)苯基]脲 Example 85-48: 1-(2-{4-[2-(2-Sideoxy-1-azetidinyl)-1,3-thiazol-5-yl]phenoxy}-5 -pyrimidinyl)-3-[2-(3-pyridyl)-5-(trifluoromethyl)phenyl]urea

TLC：Rf 0.24(氯仿：甲醇=19：1)；1H-NMR(DMSO-d6)：δ 3.24-3.27(m，2 H)，3.87(t，2 H)，7.20-7.25(m，2 H)，7.47-7.58(m，3 H)，7.63-7.69(m，2 H)，7.85(s，1 H)， 7.89(dt，1 H)，8.24(s，1 H)，8.38(s，1 H)，8.62-8.68(m，4 H)，9.24(s，1 H)。 TLC: Rf 0.24 (chloroform:methanol = 19:1); 1 H-NMR (DMSO-d 6 ): δ 3.24 - 3.27 (m, 2 H), 3.87 (t, 2 H), 7.20-7.25 (m, 2 H), 7.47-7.58 (m, 3 H), 7.63-7.69 (m, 2 H), 7.85 (s, 1 H), 7.89 (dt, 1 H), 8.24 (s, 1 H), 8.38 ( s, 1 H), 8.62 - 8.68 (m, 4 H), 9.24 (s, 1 H).

實施例85-49：1-(2-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-異丙基-5-(三氟甲基)-3-吡啶基]脲 Example 85-49: 1-(2-{4-[2-(ethylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-[2-iso Propyl-5-(trifluoromethyl)-3-pyridyl]urea

TLC：Rf 0.25(己烷：乙酸乙酯=1：4)；1H-NMR(DMSO-d6)：δ 1.14-1.25(m，9 H)，3.20-3.40(m，3 H)，7.14(d，2 H)，7.43-7.46(m，3 H)，7.72(t，1 H)，8.54(s，1 H)，8.61(s，1 H)，8.65(s，1 H)，8.72(s，2 H)，9.33(s，1 H)。 TLC: Rf 0.25 (hexane: ethyl acetate = 1 : 4); 1 H-NMR (DMSO-d 6 ): δ 1.14-1.25 (m, 9 H), 3.20-3.40 (m, 3 H), 7.14 (d, 2 H), 7.43-7.46 (m, 3 H), 7.72 (t, 1 H), 8.54 (s, 1 H), 8.61 (s, 1 H), 8.65 (s, 1 H), 8.72 (s, 2 H), 9.33 (s, 1 H).

實施例85-50：1-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-(3-吡啶基氧基)-5-(三氟甲基)苯基]脲 Example 85-50: 1-(2-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl )-3-[2-(3-pyridyloxy)-5-(trifluoromethyl)phenyl]urea

TLC：Rf 0.56(乙酸乙酯：甲醇=9：1)；1H-NMR(DMSO-d6)：δ 2.11-2.23(m，2 H)，2.64(t，2 H)，4.05(t，2 H)，7.01(d，1 H)，7.23(d，2 H)，7.32(dd，1 H)，7.49(dd，1 H)，7.64(dd，1 H)，7.68(d，2 H)，7.89(s，1 H)，8.47(d，1 H)，8.54(d，1 H)，8.65(s，1 H)，8.71(s，2 H)，9.02(s，1 H)，9.48(s，1 H)。 TLC: Rf 0.56 (ethyl acetate:methanol = 9:1); 1 H-NMR (DMSO-d 6 ): δ 2.11-2.23 (m, 2 H), 2.64 (t, 2 H), 4.05 (t, 2 H), 7.01 (d, 1 H), 7.23 (d, 2 H), 7.32 (dd, 1 H), 7.49 (dd, 1 H), 7.64 (dd, 1 H), 7.68 (d, 2 H) ), 7.89 (s, 1 H), 8.47 (d, 1 H), 8.54 (d, 1 H), 8.65 (s, 1 H), 8.71 (s, 2 H), 9.02 (s, 1 H), 9.48 (s, 1 H).

實施例85-51：1-[5-(3-氧雜環丁烷基)-2-(3-吡啶基)苯基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 85-51:1-[5-(3-oxetanyl)-2-(3-pyridyl)phenyl]-3-(2-{4-[2-(2- side oxygen) -ylpyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.52(乙酸乙酯：甲醇=9：1)；1H-NMR(DMSO-d6)：δ 2.09-2.23(m，2 H)，2.64(t，2 H)，4.05(t，2 H)，4.25-4.34(m，1 H)，4.63(t，2 H)，4.97(dd，2 H)，7.20(d，2 H)，7.27(s，2 H)，7.49(dd，1 H)，7.66(d，2 H)，7.81(d，1 H)，7.88(s，2 H)，8.08(s，1 H)，8.58(s，2 H)，8.62(s，2 H)，9.08(s，1 H)。 TLC: Rf 0.52 (ethyl acetate: methanol = 9: 1); 1 H -NMR (DMSO-d 6): δ 2.09-2.23 (m, 2 H), 2.64 (t, 2 H), 4.05 (t, 2 H), 4.25-4.34 (m, 1 H), 4.63 (t, 2 H), 4.97 (dd, 2 H), 7.20 (d, 2 H), 7.27 (s, 2 H), 7.49 (dd, 1 H), 7.66 (d, 2 H), 7.81 (d, 1 H), 7.88 (s, 2 H), 8.08 (s, 1 H), 8.58 (s, 2 H), 8.62 (s, 2 H) ), 9.08 (s, 1 H).

實施例85-52：1-(2-{3-甲基-4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-(3-吡啶基)-5-(三氟甲基)苯基]脲 Example 85-52: 1-(2-{3-methyl-4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy} -5-pyrimidinyl)-3-[2-(3-pyridyl)-5-(trifluoromethyl)phenyl]urea

TLC：Rf 0.34(乙酸乙酯：甲醇=9：1)；1H-NMR(DMSO-d6)：δ 2.11-2.24(m，2 H)，2.37(s，3 H)，2.63(t，2 H)，4.06(t，2 H)，7.05(dd，1 H)，7.14(d，1 H)，7.40(d，1 H)，7.50(d，2 H)，7.55-7.60(m，3 H)，7.89(dd，1 H)，8.24(s，1 H)，8.37(s，1 H)，8.64(s，2 H)，8.67(dd，1 H)，9.24(s，1 H)。 TLC: Rf 0.34 (ethyl acetate: methanol = 9: 1); 1 H -NMR (DMSO-d 6): δ 2.11-2.24 (m, 2 H), 2.37 (s, 3 H), 2.63 (t, 2 H), 4.06 (t, 2 H), 7.05 (dd, 1 H), 7.14 (d, 1 H), 7.40 (d, 1 H), 7.50 (d, 2 H), 7.55-7.60 (m, 3 H), 7.89 (dd, 1 H), 8.24 (s, 1 H), 8.37 (s, 1 H), 8.64 (s, 2 H), 8.67 (dd, 1 H), 9.24 (s, 1 H) ).

實施例85-53：1-(2-{3-甲基-4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[3-(三氟甲基)苯基]脲 Examples 85-53: 1-(2-{3-methyl-4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy} -5-pyrimidinyl)-3-[3-(trifluoromethyl)phenyl]urea

TLC：Rf 0.35(乙酸乙酯：甲醇=9：1)；1H-NMR(DMSO-d6)：δ 2.11-2.23(m，2 H)，2.38(s，3 H)，2.63(t，2 H)，4.06(t，2 H)，7.05(dd，1 H)，7.16(d，1 H)，7.32(dd，1 H)，7.42(d，1 H)，7.51(t，1 H)，7.57(s，1 H)，7.60(dd，1 H)，7.97(s，1 H)，8.71(s，2 H)，8.98(s，1 H)，9.31(s，1 H)。 TLC: Rf 0.35 (ethyl acetate:methanol = 9:1); 1 H-NMR (DMSO-d 6 ): δ 2.11-2.23 (m, 2 H), 2.38 (s, 3 H), 2.63 (t, 2 H), 4.06 (t, 2 H), 7.05 (dd, 1 H), 7.16 (d, 1 H), 7.32 (dd, 1 H), 7.42 (d, 1 H), 7.51 (t, 1 H) ), 7.57 (s, 1 H), 7.60 (dd, 1 H), 7.97 (s, 1 H), 8.71 (s, 2 H), 8.98 (s, 1 H), 9.31 (s, 1 H).

實施例85-54：1-[2-(4-{2-[4-(羥基甲基)-2-側氧基-1-吡咯啶基]-1，3-噻唑-5-基}苯氧基)-5-嘧啶基]-3-[2-(3-吡啶基)-5-(三氟甲基)苯基]脲 Examples 85-54: 1-[2-(4-{2-[4-(Hydroxymethyl)-2-oxo-l-pyrrolidinyl]-1,3-thiazol-5-yl}benzene Oxy)-5-pyrimidinyl]-3-[2-(3-pyridyl)-5-(trifluoromethyl)phenyl]urea

TLC：Rf 0.29(氯仿：甲醇=19：1)；1H-NMR(DMSO-d6)：δ 2.40-2.52(m，1 H)，2.59-2.81(m，2 H)，3.41-3.54(m，2 H)，3.85(dd，1 H)，4.08-4.14(m，1 H)，4.92(t，1 H)，7.18-7.25(m，2 H)，7.47-7.58(m，3 H)，7.63-7.69(m，2 H)，7.87-7.91(m，2 H)，8.23(s，1 H)，8.38(s，1 H)，8.63-8.68(m，4 H)，9.24(s，1 H)。 TLC: Rf 0.29 (chloroform:methanol = 19:1); 1 H-NMR (DMSO-d 6 ): δ 2.40-2.52 (m, 1 H), 2.59-2.81 (m, 2 H), 3.41-3.54 ( m, 2 H), 3.85 (dd, 1 H), 4.08-4.14 (m, 1 H), 4.92 (t, 1 H), 7.18-7.25 (m, 2 H), 7.47-7.58 (m, 3 H ), 7.63-7.69 (m, 2 H), 7.87-7.91 (m, 2 H), 8.23 (s, 1 H), 8.38 (s, 1 H), 8.63 - 8.68 (m, 4 H), 9.24 ( s, 1 H).

實施例85-55：1-[2-({6-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]-3-吡啶基}氧基)-5-嘧啶基]-3-[3-(三氟甲基)苯基]脲 Example 85-55: 1-[2-({6-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]-3-pyridyl}oxy )-5-pyrimidinyl]-3-[3-(trifluoromethyl)phenyl]urea

TLC：Rf 0.43(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 2.16(m，2 H)，2.64(t，2 H)，4.06(t，2 H)，7.32(d，1 H)，7.52(t，1 H)，7.61(d，1 H)，7.75(dd，1 H)，7.96(s，1 H)，8.03(d，1 H)，8.18(s，1 H)，8.46(d，1 H)，8.73(s，2 H)，9.01(s，1 H)，9.31(s，1 H)。 TLC: Rf 0.43 (ethyl acetate); 1 H-NMR (DMSO -d 6): δ 2.16 (m, 2 H), 2.64 (t, 2 H), 4.06 (t, 2 H), 7.32 (d, 1 H), 7.52 (t, 1 H), 7.61 (d, 1 H), 7.75 (dd, 1 H), 7.96 (s, 1 H), 8.03 (d, 1 H), 8.18 (s, 1 H) ), 8.46 (d, 1 H), 8.73 (s, 2 H), 9.01 (s, 1 H), 9.31 (s, 1 H).

實施例85-56：1-[2-({6-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]-3-吡啶基}氧基)-5-嘧啶基]-3-[2-(3-吡啶基)-5-(三氟甲基)苯基]脲 Example 85-56: 1-[2-({6-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]-3-pyridyl}oxy )-5-pyrimidinyl]-3-[2-(3-pyridyl)-5-(trifluoromethyl)phenyl]urea

TLC：Rf 0.36(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 2.16(m，2 H)，2.64(t，2 H)，4.05(t，2 H)，7.46-7.60(m，3 H)，7.73(dd，1 H)，7.87-7.93(m，1 H)，8.02(d，1 H)，8.17(s，1 H)，8.24(s，1 H)，8.37(s，1 H)，8.44(d，1 H)， 8.63-8.74(m，4 H)，9.26(s，1 H)。 TLC: Rf 0.36 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 2.16 (m, 2 H), 2.64 (t, 2 H), 4.05 (t, 2 H), 7.46-7. m,3 H), 7.73 (dd, 1 H), 7.87-7.93 (m, 1 H), 8.02 (d, 1 H), 8.17 (s, 1 H), 8.24 (s, 1 H), 8.37 ( s, 1 H), 8.44 (d, 1 H), 8.63-8.74 (m, 4 H), 9.26 (s, 1 H).

實施例85-57：1-(2-{4-[2-(二甲胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[3-(三氟甲基)苯基]脲 Example 85-57: 1-(2-{4-[2-(Dimethylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-[3- (trifluoromethyl)phenyl]urea

TLC：Rf 0.44(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 3.07(s，6 H)，7.15(d，2 H)，7.31(d，1 H)，7.45-7.66(m，5 H)，7.96(s，1 H)，8.70(s，2 H)，8.95(s，1 H)，9.28(s，1 H)。 TLC: Rf 0.44 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 3.07 (s, 6 H), 7.15 (d, 2 H), 7.31 (d, 1 H), 7.45-7. m, 5 H), 7.96 (s, 1 H), 8.70 (s, 2 H), 8.95 (s, 1 H), 9.28 (s, 1 H).

實施例85-58：1-[2-(環丙基羰基)-5-(三氟甲基)-3-吡啶基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 85-58: 1-[2-(Cyclopropylcarbonyl)-5-(trifluoromethyl)-3-pyridyl]-3-(2-{4-[2-(2-trioxy) -1-pyrrolidyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.59(乙酸乙酯)；1H-NMR(CDCl3)：δ 1.25(d，4 H)，2.30(m，2 H)，2.75(t，2 H)，3.74(m，1 H)，4.20(t，2 H)，7.24(d，2 H)，7.31(s，1 H)，7.58(s，1 H)，7.62(d，2 H)，8.59(s，1 H)，8.73(s，2 H)，9.28(s，1 H)，11.5(s，1 H)。 TLC: Rf 0.59 (ethyl acetate); 1 H-NMR (CDCl 3 ): δ 1.25 (d, 4 H), 2.30 (m, 2 H), 2.75 (t, 2 H), 3.74 (m, 1 H) ), 4.20 (t, 2 H), 7.24 (d, 2 H), 7.31 (s, 1 H), 7.58 (s, 1 H), 7.62 (d, 2 H), 8.59 (s, 1 H), 8.73 (s, 2 H), 9.28 (s, 1 H), 11.5 (s, 1 H).

實施例85-59：1-(2-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[4-甲基-3-(三氟甲基)苯基]脲 Examples 85-59: 1-(2-{4-[2-(ethylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-[4- 3-(trifluoromethyl)phenyl]urea

TLC：Rf 0.29(氯仿：甲醇=10：1)；1H-NMR(DMSO-d6)：δ 1.16(t，3 H)，2.36(s，3 H)，3.20-3.32(m，2 H)，7.14(d，2 H)，7.33(d，1 H)，7.41-7.48(m，3 H)，7.51-7.56(m，1 H)，7.72(t，1 H)，7.87-7.90(m，1 H)，8.69(s，2 H)，8.94(s，1 H)，9.20(s，1 H)。 TLC: Rf 0.29 (chloroform:methanol = 10:1); 1 H-NMR (DMSO-d 6 ): δ 1.16 (t, 3 H), 2.36 (s, 3 H), 3.20-3.32 (m, 2 H) ), 7.14 (d, 2 H), 7.33 (d, 1 H), 7.41-7.48 (m, 3 H), 7.51-7.56 (m, 1 H), 7.72 (t, 1 H), 7.87-7.90 ( m, 1 H), 8.69 (s, 2 H), 8.94 (s, 1 H), 9.20 (s, 1 H).

實施例85-60：1-(2-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[4-(三氟甲基)苯基]脲 Example 85-60: 1-(2-{4-[2-(ethylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-[4-( Trifluoromethyl)phenyl]urea

TLC：Rf 0.18(氯仿：甲醇=10：1)；1H-NMR(DMSO-d6)：δ 1.17(t，3 H)，3.21-3.34(m，2 H)，7.14(d，2 H)，7.42-7.49(m，3 H)，7.60-7.75(m，5 H)，8.71(s，2 H)，9.12(s，1 H)，9.49(s，1 H)。 TLC: Rf 0.18 (chloroform:methanol = 10:1); 1 H-NMR (DMSO-d 6 ): δ 1.17 (t, 3 H), 3.21-3.34 (m, 2 H), 7.14 (d, 2 H) ), 7.42-7.49 (m, 3 H), 7.60-7.75 (m, 5 H), 8.71 (s, 2 H), 9.12 (s, 1 H), 9.49 (s, 1 H).

實施例85-61：1-(2-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[3-氟-5-(三氟甲基)苯基]脲 Example 85-61:1-(2-{4-[2-(ethylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-[3-fluoro -5-(trifluoromethyl)phenyl]urea

TLC：Rf 0.16(氯仿：甲醇=10：1)；1H-NMR(DMSO-d6)：δ 1.17(t，3 H)，3.21-3.31(m，2 H)，7.12-7.18(m，2 H)，7.22-7.28(m，1 H)，7.42-7.49(m，3 H)，7.59-7.66(m，1 H)，7.68-7.75(m，2 H)，8.70(s，2 H)，9.10(s，1 H)，9.52(s，1 H)。 TLC: Rf 0.16 (chloroform:methanol = 10:1); 1 H-NMR (DMSO-d 6 ): δ 1.17 (t, 3 H), 3.21-3.31 (m, 2 H), 7.12 to 7.18 (m, 2 H), 7.22-7.28 (m, 1 H), 7.42-7.49 (m, 3 H), 7.59-7.66 (m, 1 H), 7.68-7.75 (m, 2 H), 8.70 (s, 2 H) ), 9.10 (s, 1 H), 9.52 (s, 1 H).

實施例85-62：1-[2-氯-5-(三氟甲基)苯基]-3-(2-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 85-62: 1-[2-Chloro-5-(trifluoromethyl)phenyl]-3-(2-{4-[2-(ethylamino)-1,3-thiazole-5- Phenyloxy-5-pyrimidinyl)urea

TLC：Rf 0.16(氯仿：甲醇=10：1)； 1H-NMR(DMSO-d6)：δ 1.17(t，3 H)，3.22-3.34(m，2 H)，7.12-7.18(m，2 H)，7.36-7.48(m，4 H)，7.67-7.76(m，2 H)，8.55(d，1 H)，8.72(s，2 H)，8.83(s，1 H)，9.81(s，1 H)。 TLC: Rf 0.16 (chloroform:methanol = 10:1); 1 H-NMR (DMSO-d 6 ): δ 1.17 (t, 3 H), 3.22-3.34 (m, 2 H), 7.12 to 7.18 (m, 2 H), 7.36-7.48 (m, 4 H), 7.67-7.76 (m, 2 H), 8.55 (d, 1 H), 8.72 (s, 2 H), 8.83 (s, 1 H), 9.81 ( s, 1 H).

實施例85-63：1-[2-氯-4-(三氟甲基)苯基]-3-(2-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Examples 85-63: 1-[2-Chloro-4-(trifluoromethyl)phenyl]-3-(2-{4-[2-(ethylamino)-1,3-thiazole-5- Phenyloxy-5-pyrimidinyl)urea

TLC：Rf 0.18(氯仿：甲醇=10：1)；1H-NMR(DMSO-d6)：δ 1.17(t，3 H)，3.20-3.34(m，2 H)，7.12-7.18(m，2 H)，7.42-7.48(m，3 H)，7.65-7.76(m，2 H)，7.86-7.90(m，1 H)，8.42(d，1 H)，8.72(s，2 H)，8.80(s，1 H)，9.80(s，1 H)。 TLC: Rf 0.18 (chloroform:methanol = 10:1); 1 H-NMR (DMSO-d 6 ): δ 1.17 (t, 3 H), 3.20-3.34 (m, 2 H), 7.12 to 7.18 (m, 2 H), 7.42-7.48 (m, 3 H), 7.65-7.76 (m, 2 H), 7.86-7.90 (m, 1 H), 8.42 (d, 1 H), 8.72 (s, 2 H), 8.80 (s, 1 H), 9.80 (s, 1 H).

實施例85-64：1-(2-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-氟-3-(三氟甲基)苯基]脲 Example 85-64: 1-(2-{4-[2-(ethylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-[2-fluoro -3-(trifluoromethyl)phenyl]urea

TLC：Rf 0.24(氯仿：甲醇=10：1)；1H-NMR(DMSO-d6)：δ 1.16(t，3 H)，3.20-3.34(m，2 H)，7.12-7.18(m，2 H)，7.32-7.48(m，5 H)，7.72(t，1 H)，8.33-8.40(m，1 H)，8.72(s，2 H)，9.03(s，1 H)，9.28(s，1 H)。 TLC: Rf 0.24 (chloroform:methanol = 10:1); 1 H-NMR (DMSO-d 6 ): δ 1.16 (t, 3 H), 3.20-3.34 (m, 2 H), 7.12 to 7.18 (m, 2 H), 7.32-7.48 (m, 5 H), 7.72 (t, 1 H), 8.33-8.40 (m, 1 H), 8.72 (s, 2 H), 9.03 (s, 1 H), 9.28 ( s, 1 H).

實施例85-65：1-(2-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-氟-5-(三氟甲基)苯基]脲 Example 85-65: 1-(2-{4-[2-(ethylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-[2-fluoro -5-(trifluoromethyl)phenyl]urea

TLC：Rf 0.24(氯仿：甲醇=10：1)；1H-NMR(DMSO-d6)：δ 1.16(t，3 H)，3.20-3.34(m，2 H)，7.11-7.18(m，2 H)，7.34-7.54(m，5 H)，7.72(t，1 H)，8.50-8.55(m，1 H)，8.71(s，2 H)，9.14(s，1 H)，9.43(s，1 H)。 TLC: Rf 0.24 (chloroform:methanol = 10:1); 1 H-NMR (DMSO-d 6 ): δ 1.16 (t, 3 H), 3.20-3.34 (m, 2 H), 7.11-7.18 (m, 2 H), 7.34 - 7.54 (m, 5 H), 7.72 (t, 1 H), 8.50-8.55 (m, 1 H), 8.71 (s, 2 H), 9.14 (s, 1 H), 9.43 ( s, 1 H).

實施例85-66：1-[2-(3-氧雜環丁烷基)-5-(三氟甲基)苯基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 85-66: 1-[2-(3-oxetanyl)-5-(trifluoromethyl)phenyl]-3-(2-{4-[2-(2- side oxygen) -ylpyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.64(乙酸乙酯：甲醇=19：1)；1H-NMR(DMSO-d6)：δ 2.10-2.20(m，2 H)，2.49-2.64(m，2 H)，4.05(t，2 H)，4.40-4.60(m，1 H)，4.64(t，2 H)，4.96(t，2 H)，7.22(d，2 H)，7.52(d，1 H)，7.65-7.72(m，3 H)，7.89(s，1 H)，7.97(s，1 H)，8.34(s，1 H)，8.71(s，2 H)，9.19(s，1 H)。 TLC: Rf 0.64 (ethyl acetate:methanol = 19:1); 1 H-NMR (DMSO-d 6 ): δ 2.10-2.20 (m, 2 H), 2.49 - 2.64 (m, 2 H), 4.05 ( t,2 H), 4.40-4.60 (m, 1 H), 4.64 (t, 2 H), 4.96 (t, 2 H), 7.22 (d, 2 H), 7.52 (d, 1 H), 7.65- 7.72 (m, 3 H), 7.89 (s, 1 H), 7.97 (s, 1 H), 8.34 (s, 1 H), 8.71 (s, 2 H), 9.19 (s, 1 H).

實施例85-67：1-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-(1H-吡唑-1-基)-5-(三氟甲基)苯基]脲 Example 85-67: 1-(2-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl )-3-[2-(1H-pyrazol-1-yl)-5-(trifluoromethyl)phenyl]urea

TLC：Rf 0.34(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 2.16(m，2 H)，2.64(t，2 H)，4.05(t，2 H)，6.73(t，1 H)，7.23(d，2 H)，7.52(dd，1 H)，7.67(d，2 H)，7.75(d，1 H)，7.89(s，1 H)，7.95(d，1 H)，8.41(d，1 H)，8.57-8.61(m，1 H)，8.69(s，2 H)，9.70(s，1 H)，9.96(s，1 H)。 TLC: Rf 0.34 (ethyl acetate); 1 H-NMR (DMSO -d 6): δ 2.16 (m, 2 H), 2.64 (t, 2 H), 4.05 (t, 2 H), 6.73 (t, 1 H), 7.23 (d, 2 H), 7.52 (dd, 1 H), 7.67 (d, 2 H), 7.75 (d, 1 H), 7.89 (s, 1 H), 7.95 (d, 1 H) ), 8.41 (d, 1 H), 8.57-8.61 (m, 1 H), 8.69 (s, 2 H), 9.70 (s, 1 H), 9.96 (s, 1 H).

實施例85-68：1-[5-氟-2-(1H-咪唑-1-基)苯基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 85-68: 1-[5-Fluoro-2-(1H-imidazol-1-yl)phenyl]-3-(2-{4-[2-(2-o-oxy-1-pyrrolidine) -1,3-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.33(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 2.17(t，2 H)，2.62-2.68(m，2 H)，4.06(t，2 H)，6.99-7.38(m，6 H)，7.67(d，2 H)，7.75-7.90(m，2 H)，7.99-8.10(m，2 H)，8.65(s，2 H)，9.43(s，1 H)。 TLC: Rf 0.33 (ethyl acetate); 1 H-NMR (DMSO -d 6): δ 2.17 (t, 2 H), 2.62-2.68 (m, 2 H), 4.06 (t, 2 H), 6.99- 7.38 (m, 6 H), 7.67 (d, 2 H), 7.75-7.90 (m, 2 H), 7.99-8.10 (m, 2 H), 8.65 (s, 2 H), 9.43 (s, 1 H) ).

實施例85-69：1-(2-{4-[2-(3-側氧基-4-嗎啉基)-1，3-噻唑-5- 基]苯氧基}-5-嘧啶基)-3-[3-(三氟甲基)苯基]脲 Examples 85-69: 1-(2-{4-[2-(3-Sideoxy-4-morpholinyl)-1,3-thiazole-5- Phenyloxy}-5-pyrimidinyl-3-[3-(trifluoromethyl)phenyl]urea

TLC：Rf 0.68(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 4.04-4.14(m，4 H)，4.41(s，2 H)，7.21-7.27(m，2 H)，7.29-7.34(m，1 H)，7.51(t，1 H)，7.58-7.64(m，1 H)，7.66-7.72(m，2 H)，7.94-7.98(m，2 H)，8.71(s，2 H)，9.06(s，1 H)，9.38(s，1 H)。 TLC: Rf 0.68 (ethyl acetate); 1 H-NMR (DMSO -d 6): δ 4.04-4.14 (m, 4 H), 4.41 (s, 2 H), 7.21-7.27 (m, 2 H), 7.29-7.34 (m, 1 H), 7.51 (t, 1 H), 7.58-7.64 (m, 1 H), 7.66-7.72 (m, 2 H), 7.94-7.98 (m, 2 H), 8.71 ( s, 2 H), 9.06 (s, 1 H), 9.38 (s, 1 H).

實施例85-70：1-[2-(4-{2-[(3-羥基丙基)胺基]-1，3-噻唑-5-基}苯氧基)-5-嘧啶基]-3-[3-(三氟甲基)苯基]脲 Example 85-70: 1-[2-(4-{2-[(3-Hydroxypropyl)amino]-1,3-thiazol-5-yl}phenoxy)-5-pyrimidinyl]- 3-[3-(trifluoromethyl)phenyl]urea

TLC：Rf 0.51(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 1.91(m，2 H)，3.34(t，2 H)，4.17(t，2 H)，7.14(d，2 H)，7.31(d，1 H)，7.43(s，1 H)，7.44(d，2 H)，7.53(t，1 H)，7.60(d，1 H)，7.80(t，1 H)，7.96(s，1 H)，8.22(s，1 H)，8.70(s，2 H)，8.95(s，1 H)，9.29(s，1 H)。 TLC: Rf 0.51 (ethyl acetate); 1 H-NMR (DMSO -d 6): δ 1.91 (m, 2 H), 3.34 (t, 2 H), 4.17 (t, 2 H), 7.14 (d, 2 H), 7.31 (d, 1 H), 7.43 (s, 1 H), 7.44 (d, 2 H), 7.53 (t, 1 H), 7.60 (d, 1 H), 7.80 (t, 1 H) ), 7.96 (s, 1 H), 8.22 (s, 1 H), 8.70 (s, 2 H), 8.95 (s, 1 H), 9.29 (s, 1 H).

實施例85-71：1-(2-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[3-(三氟甲基)苯基]脲 Example 85-71:1-(2-{4-[2-(propylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-[3-(three Fluoromethyl)phenyl]urea

TLC：Rf 0.68(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 0.91(m，3 H)，1.58(m，2 H)，3.19(q，2 H)，7.14(d，2 H)，7.32(d，1 H)，7.41-7.57(m，4 H)，7.61(d，1 H)， 7.75(t，1 H)，7.96(s，1 H)，8.69(s，2 H)，8.96(s，1 H)，9.29(s，1 H)。 TLC: Rf 0.68 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 0.91 (m, 3 H), 1.58 (m, 2 H), 3.19 (q, 2 H), 7.14 (d, 2 H), 7.32 (d, 1 H), 7.41-7.57 (m, 4 H), 7.61 (d, 1 H), 7.75 (t, 1 H), 7.96 (s, 1 H), 8.69 (s, 2 H), 8.96 (s, 1 H), 9.29 (s, 1 H).

實施例85-72：1-[2-(4-{2-[(2-羥基乙基)胺基]-1，3-噻唑-5-基}苯氧基)-5-嘧啶基]-3-[3-(三氟甲基)苯基]脲 Example 85-72: 1-[2-(4-{2-[(2-Hydroxyethyl)amino]-1,3-thiazol-5-yl}phenoxy)-5-pyrimidinyl]- 3-[3-(trifluoromethyl)phenyl]urea

TLC：Rf 0.35(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 3.28-3.38(m，2 H)，3.55(q，2 H)，4.76(t，1 H)，7.14(d，2 H)，7.31(d，1 H)，7.41-7.56(m，4 H)，7.61(d，1 H)，7.75(t，1 H)，7.96(s，1 H)，8.69(s，2 H)，8.95(s，1 H)，9.28(s，1 H)。 TLC: Rf 0.35 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 3.28 - 3.38 (m, 2 H), 3.55 (q, 2 H), 4.76 (t, 1 H), 7.14 ( d, 2 H), 7.31 (d, 1 H), 7.41-7.56 (m, 4 H), 7.61 (d, 1 H), 7.75 (t, 1 H), 7.96 (s, 1 H), 8.69 ( s, 2 H), 8.95 (s, 1 H), 9.28 (s, 1 H).

實施例85-73：1-(2-{4-[2-(丁胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[3-(三氟甲基)苯基]脲 Examples 85-73: 1-(2-{4-[2-(butylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-[3-( Trifluoromethyl)phenyl]urea

TLC：Rf 0.80(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 0.90(t，3 H)，1.36(m，2 H)，1.54(m，2 H)，3.24(q，2 H)，7.14(d，2 H)，7.31(d，1 H)，7.41-7.57(m，4 H)，7.60(d，1 H)，7.72(t，1 H)，7.96(s，1 H)，8.69(s，2 H)，8.96(s，1 H)，9.29(s，1 H)。 TLC: Rf 0.80 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 0.90 (t, 3 H), 1.36 (m, 2 H), 1.54 (m, 2 H), 3.24 (q, 2 H), 7.14 (d, 2 H), 7.31 (d, 1 H), 7.41-7.57 (m, 4 H), 7.60 (d, 1 H), 7.72 (t, 1 H), 7.96 (s, 1 H), 8.69 (s, 2 H), 8.96 (s, 1 H), 9.29 (s, 1 H).

實施例85-74：1-{2-[4-(2-{[2-(4-嗎啉基)乙基]胺基}-1，3-噻唑-5-基)苯氧基]-5-嘧啶基}-3-[3-(三氟甲基)苯基]脲 Examples 85-74: 1-{2-[4-(2-{[2-(4-morpholinyl)ethyl]amino}-1,3-thiazol-5-yl)phenoxy]- 5-pyrimidinyl}-3-[3-(trifluoromethyl)phenyl]urea

TLC：Rf 0.57(乙酸乙酯：甲醇=9：1)；1H-NMR(DMSO-d6)：δ 2.49(m，6 H)，3.39(q，2 H)，3.57(t，4 H)， 7.14(d，2 H)，7.32(d，1 H)，7.40-7.55(m，4 H)，7.58-7.73(m，2 H)，7.96(s，1 H)，8.69(s，2 H)，8.96(s，1 H)，9.29(s，1 H)。 TLC: Rf 0.57 (ethyl acetate: methanol = 9: 1); 1 H -NMR (DMSO-d 6): δ 2.49 (m, 6 H), 3.39 (q, 2 H), 3.57 (t, 4 H ), 7.14 (d, 2 H), 7.32 (d, 1 H), 7.40-7.55 (m, 4 H), 7.58-7.73 (m, 2 H), 7.96 (s, 1 H), 8.69 (s, 2 H), 8.96 (s, 1 H), 9.29 (s, 1 H).

實施例85-75：1-[2-(4-甲基-1H-咪唑-1-基)-5-(三氟甲基)苯基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 85-75: 1-[2-(4-Methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl]-3-(2-{4-[2-( 2-sided oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.38(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 2.16(m，2 H)，2.20(s，3 H)，2.64(t，2 H)，4.04(t，2 H)，7.16(s，1 H)，7.22(d，2 H)，7.46-7.55(m，2 H)，7.67(d，2 H)，7.81(s，1 H)，7.89(s，1 H)，8.33(s，1 H)，8.51(s，1 H)，8.66(s，2 H)，9.43(s，1 H)。 TLC: Rf 0.38 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 2.16 (m, 2 H), 2.20 (s, 3 H), 2.64 (t, 2 H), 4.04 (t, 2 H), 7.16 (s, 1 H), 7.22 (d, 2 H), 7.46-7.55 (m, 2 H), 7.67 (d, 2 H), 7.81 (s, 1 H), 7.89 (s, 1 H), 8.33 (s, 1 H), 8.51 (s, 1 H), 8.66 (s, 2 H), 9.43 (s, 1 H).

實施例85-76：1-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-(1H-1，2，3-三唑-1-基)-5-(三氟甲基)苯基]脲 Example 85-76: 1-(2-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl )-3-[2-(1H-1,2,3-triazol-1-yl)-5-(trifluoromethyl)phenyl]urea

TLC：Rf 0.54(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 2.16(m，2 H)，2.64(t，2 H)，4.05(t，2 H)，7.22(d，2 H)，7.58-7.78(m，4 H)，7.89(s，1 H)，8.09(s，1 H)，8.57(s，1 H)，8.64-8.75(m，4 H)，9.64(s，1 H)。 TLC: Rf 0.54 (ethyl acetate); 1 H-NMR (DMSO -d 6): δ 2.16 (m, 2 H), 2.64 (t, 2 H), 4.05 (t, 2 H), 7.22 (d, 2 H), 7.58-7.78 (m, 4 H), 7.89 (s, 1 H), 8.09 (s, 1 H), 8.57 (s, 1 H), 8.64 - 8.75 (m, 4 H), 9.64 ( s, 1 H).

實施例85-77：1-[2-(4-{2-[3-(2-羥基-2-丙基)-2-側氧基-1-吡咯啶基]-1，3-噻唑-5-基}苯氧基)-5-嘧啶基]-3-[2-(3-吡啶基)-5-(三氟甲基)苯基]脲 Example 85-77: 1-[2-(4-{2-[3-(2-hydroxy-2-propyl)-2-oxo-l-pyrrolidinyl]-1,3-thiazole- 5-yl}phenoxy)-5-pyrimidinyl]-3-[2-(3-pyridyl)-5-(trifluoromethyl)phenyl]urea

TLC：Rf 0.51(乙酸乙酯：甲醇=9：1)；1H-NMR(CDCl3)：δ 1.29(s，3 H)，1.35(s，3 H)，1.99-2.14(m，1 H)，2.33-2.46(m，1 H)，2.93(t，1 H)，3.85-4.02(m，2 H)，4.21-4.33(m，1 H)，7.14-7.25(m，3 H)，7.36-7.47(m，3 H)，7.51-7.63(m，3 H)， 7.78-7.84(m，1 H)，8.21-8.26(m，1 H)，8.43(s，1 H)，8.57(s，2 H)，8.68(s，1 H)，8.90(s，1 H)。 TLC: Rf 0.51 (ethyl acetate:methanol = 9:1); 1 H-NMR (CDCl 3 ): δ 1.29 (s, 3 H), 1.35 (s, 3 H), 1.99-2.14 (m, 1 H) ), 2.33 - 2.46 (m, 1 H), 2.93 (t, 1 H), 3.85-4.02 (m, 2 H), 4.21-4.33 (m, 1 H), 7.14 - 7.25 (m, 3 H), 7.36-7.47 (m, 3 H), 7.51-7.63 (m, 3 H), 7.78-7.84 (m, 1 H), 8.21-8.26 (m, 1 H), 8.43 (s, 1 H), 8.57 ( s, 2 H), 8.68 (s, 1 H), 8.90 (s, 1 H).

實施例85-78：1-[2-(4-{2-[3-(2-羥基-2-丙基)-2-側氧基-1-吡咯啶基]-1，3-噻唑-5-基}苯氧基)-5-嘧啶基]-3-[3-(三氟甲基)苯基]脲 Example 85-78: 1-[2-(4-{2-[3-(2-hydroxy-2-propyl)-2-oxo-l-pyrrolidinyl]-1,3-thiazole- 5-yl}phenoxy)-5-pyrimidinyl]-3-[3-(trifluoromethyl)phenyl]urea

TLC：Rf 0.17(己烷：乙酸乙酯=1：4)；1H-NMR(CDCl3+CD3OD)：δ 1.26(s，3 H)，1.30(s，3 H)，1.95-2.13(m，1 H)，2.30-2.42(m，1 H)，2.89(t，1 H)，3.87-3.97(m，1 H)，4.15-4.25(m，1 H)，7.14-7.27(m，3 H)，7.37(t，1 H)，7.52-7.66(m，5 H)，8.64(s，2 H)。 TLC: Rf 0.17 (hexane: ethyl acetate = 1 : 4); 1 H-NMR (CDCl 3 + CD 3 OD): δ 1.26 (s, 3 H), 1.30 (s, 3 H), 1.95-2. (m, 1 H), 2.30-2.42 (m, 1 H), 2.89 (t, 1 H), 3.87-3.97 (m, 1 H), 4.15-4.25 (m, 1 H), 7.14-7.27 (m) , 3 H), 7.37 (t, 1 H), 7.52-7.66 (m, 5 H), 8.64 (s, 2 H).

實施例85-79：1-[2-(2-甲基-1H-咪唑-1-基)-5-(三氟甲基)苯基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 85-79: 1-[2-(2-Methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl]-3-(2-{4-[2-( 2-sided oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.45(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 2.12(s，3 H)，2.16(m，2 H)，2.64(t，2 H)，4.05(t，2 H)，7.04(d，1 H)，7.20-7.29(m，3 H)，7.46-7.57(m，2 H)，7.67(d，2 H)，7.89(s，1 H)，8.19(s，1 H)，8.64(s，1 H)，8.66(s，2 H)，9.48(s，1 H)。 TLC: Rf 0.45 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 2.12 (s, 3 H), 2.16 (m, 2 H), 2.64 (t, 2 H), 4.05 (t, 2 H), 7.04 (d, 1 H), 7.20-7.29 (m, 3 H), 7.46-7.57 (m, 2 H), 7.67 (d, 2 H), 7.89 (s, 1 H), 8.19 ( s, 1 H), 8.64 (s, 1 H), 8.66 (s, 2 H), 9.48 (s, 1 H).

實施例85-80：1-[2-(4-(2-[(2-羥基丙基)胺基]-1，3-噻唑-5-基}苯氧基)-5-嘧啶基]-3-[3-(三氟甲基)苯基]脲 Example 85-80: 1-[2-(4-(2-[(2-Hydroxypropyl)amino]-1,3-thiazol-5-yl}phenoxy)-5-pyrimidinyl]- 3-[3-(trifluoromethyl)phenyl]urea

TLC：Rf 0.54(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 1.08(d，3 H)，3.18(t，2 H)，3.81(m，1 H)，4.78(d，1 H)，7.14(d，2 H)，7.32(d，1 H)，7.42(s，1 H)，7.45(d，2 H)，7.53(t，1 H)，7.62(d，1 H)，7.76(t，1 H)，7.97(s，1 H)，8.69(s，2 H)，8.98(s，1 H)，9.31(s，1 H)。 TLC: Rf 0.54 (ethyl acetate); 1 H-NMR (DMSO -d 6): δ 1.08 (d, 3 H), 3.18 (t, 2 H), 3.81 (m, 1 H), 4.78 (d, 1 H), 7.14 (d, 2 H), 7.32 (d, 1 H), 7.42 (s, 1 H), 7.45 (d, 2 H), 7.53 (t, 1 H), 7.62 (d, 1 H) ), 7.76 (t, 1 H), 7.97 (s, 1 H), 8.69 (s, 2 H), 8.98 (s, 1 H), 9.31 (s, 1 H).

實施例85-81：1-[3-(二氟甲基)苯基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 85-81:1-[3-(Difluoromethyl)phenyl]-3-(2-{4-[2-(2-o-oxy-1-pyrrolidinyl)-1,3- Thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.30(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 2.12-2.21(m，2 H)，2.64(t，2 H)，4.05(t，2 H)，6.81-7.24(m，4 H)，7.41(t，1 H)，7.51(d，1 H)，7.64-7.69(m，2 H)，7.77(s，1 H)，7.89(s，1 H)，8.71(s，2 H)，8.90(s，1 H)，9.16(s，1 H)。 TLC: Rf 0.30 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 2.12-2.21 (m, 2 H), 2.64 (t, 2 H), 4.05 (t, 2 H), 6.81 7.24 (m, 4 H), 7.41 (t, 1 H), 7.51 (d, 1 H), 7.64-7.69 (m, 2 H), 7.77 (s, 1 H), 7.89 (s, 1 H), 8.71 (s, 2 H), 8.90 (s, 1 H), 9.16 (s, 1 H).

實施例85-82：1-[3-(1，1-二氟乙基)苯基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 85-82: 1-[3-(1,1-Difluoroethyl)phenyl]-3-(2-{4-[2-(2-o-oxy-1-pyrrolidinyl)- 1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.30(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 1.93(t，3 H)，2.11-2.21(m，2 H)，2.64(t，2 H)，4.05(t，2 H)，7.15(d，1 H)，7.22(d，2 H)，7.38(t，1 H)，7.49(d，1 H)，7.66(d，2 H)，7.72(s，1 H)，7.89(s，1 H)，8.71(s，2 H)，8.89(s，1 H)，9.13(s，1 H)。 TLC: Rf 0.30 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 1.93 (t, 3 H), 2.11-2.21 (m, 2 H), 2.64 (t, 2 H), 4.05 ( t, 2 H), 7.15 (d, 1 H), 7.22 (d, 2 H), 7.38 (t, 1 H), 7.49 (d, 1 H), 7.66 (d, 2 H), 7.72 (s, 1 H), 7.89 (s, 1 H), 8.71 (s, 2 H), 8.89 (s, 1 H), 9.13 (s, 1 H).

實施例85-83：1-[3-(二氟甲基)苯基]-3-(2-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 85-83: 1-[3-(Difluoromethyl)phenyl]-3-(2-{4-[2-(ethylamino)-1,3-thiazol-5-yl]phenoxy }-5-pyrimidinyl)urea

TLC：Rf 0.56(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 1.17(t，3 H)，3.21-3.27(m，2 H)，6.81-7.18(m，4 H)，7.39-7.53(m，5 H)，7.72(t，1 H)，7.77(s，1 H)，8.71(s，2 H)，8.89(s，1 H)，9.15(s，1 H)。 TLC: Rf 0.56 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 1.17 (t, 3 H), 3.21-3.27 (m, 2 H), 6.81-7.18 (m, 4 H), 7.39-7.53 (m, 5 H), 7.72 (t, 1 H), 7.77 (s, 1 H), 8.71 (s, 2 H), 8.89 (s, 1 H), 9.15 (s, 1 H).

實施例85-84：1-(3-乙醯基苯基)-3-(2-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 85-84: 1-(3-Ethylphenyl)-3-(2-{4-[2-(ethylamino)-1,3-thiazol-5-yl]phenoxy}- 5-pyrimidinyl urea

TLC：Rf 0.52(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 1.18(t，3 H)，2.56(s，3 H)，3.22-3.30(m，2 H)，7.13-7.17(m，2 H)，7.42-7.47(m，4 H)，7.59-7.63(m，1 H)，7.74-7.68(m，2 H)，8.03(t，1 H)，8.71(s，2 H)，8.89(s，1 H)，9.17(s，1 H)。 TLC: Rf 0.52 (ethyl acetate); 1 H-NMR (DMSO -d 6): δ 1.18 (t, 3 H), 2.56 (s, 3 H), 3.22-3.30 (m, 2 H), 7.13- 7.17 (m, 2 H), 7.42-7.47 (m, 4 H), 7.59-7.63 (m, 1 H), 7.74-7.68 (m, 2 H), 8.03 (t, 1 H), 8.71 (s, 2 H), 8.89 (s, 1 H), 9.17 (s, 1 H).

實施例85-85：1-(2-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-(3-氟苯基)脲 Example 85-85: 1-(2-{4-[2-(ethylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-(3-fluoro Phenyl)urea

TLC：Rf 0.32(氯仿：甲醇=10：1)；1H-NMR(DMSO-d6)：δ 1.16(t，3 H)，3.21-3.32(m，2 H)，6.79(td，1 H)，7.11-7.17(m，3 H)，7.26-7.34(m，1 H)，7.42-7.49(m，4 H)，7.72(t，1 H)，8.69(s，2 H)，8.90(s，1 H)，9.16(s，1 H)。 TLC: Rf 0.32 (chloroform:methanol = 10:1); 1 H-NMR (DMSO-d 6 ): δ 1.16 (t, 3 H), 3.21-3.32 (m, 2 H), 6.79 (td, 1 H) ), 7.11-7.17 (m, 3 H), 7.26-7.34 (m, 1 H), 7.42-7.49 (m, 4 H), 7.72 (t, 1 H), 8.69 (s, 2 H), 8.90 ( s, 1 H), 9.16 (s, 1 H).

實施例85-86：1-[4-氯-3-(三氟甲基)苯基]-3-(2-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 85-86: 1-[4-Chloro-3-(trifluoromethyl)phenyl]-3-(2-{4-[2-(ethylamino)-1,3-thiazole-5- Phenyloxy-5-pyrimidinyl)urea

TLC：Rf 0.29(氯仿：甲醇=10：1)；1H-NMR(DMSO-d6)：δ 1.16(t，3 H)，3.20-3.32(m，2 H)，7.14(d，2 H)，7.41-7.48(m，3 H)，7.59-7.74(m，3 H)，8.04-8.08(m，1 H)，8.69(s，2 H)，9.03(s，1 H)，9.43(s，1 H)。 TLC: Rf 0.29 (chloroform:methanol = 10:1); 1 H-NMR (DMSO-d 6 ): δ 1.16 (t, 3 H), 3.20-3.32 (m, 2 H), 7.14 (d, 2 H) ), 7.41-7.48 (m, 3 H), 7.59-7.74 (m, 3 H), 8.04-8.08 (m, 1 H), 8.69 (s, 2 H), 9.03 (s, 1 H), 9.43 ( s, 1 H).

實施例85-87：1-(2-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-甲基-5-(三氟甲基)苯基]脲 Example 85-87: 1-(2-{4-[2-(ethylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-[2- 5--5-(trifluoromethyl)phenyl]urea

TLC：Rf 0.29(氯仿：甲醇=10：1)；1H-NMR(DMSO-d6)：δ 1.16(t，3 H)，2.34(s，3 H)，3.20-3.32(m，2 H)，7.10-7.18(m，2 H)，7.24-7.30(m，1 H)，7.36-7.48(m，4 H)，7.68-7.76(m，1 H)，8.20(s，1 H)，8.74(s，2 H)，9.17(s，1 H)，10.4(s，1 H)。 TLC: Rf 0.29 (chloroform:methanol = 10:1); 1 H-NMR (DMSO-d 6 ): δ 1.16 (t, 3 H), 2.34 (s, 3 H), 3.20-3.32 (m, 2 H) ), 7.10-7.18 (m, 2 H), 7.24-7.30 (m, 1 H), 7.36-7.48 (m, 4 H), 7.68-7.76 (m, 1 H), 8.20 (s, 1 H), 8.74 (s, 2 H), 9.17 (s, 1 H), 10.4 (s, 1 H).

實施例85-88：1-[3-氯-5-(三氟甲基)苯基]-3-(2-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 85-88: 1-[3-Chloro-5-(trifluoromethyl)phenyl]-3-(2-{4-[2-(ethylamino)-1,3-thiazole-5- Phenyloxy-5-pyrimidinyl)urea

TLC：Rf 0.32(氯仿：甲醇=10：1)；1H-NMR(DMSO-d6)：δ 1.17(t，3 H)，3.20-3.33(m，2 H)，7.14(d， 2 H)，7.38-7.49(m，4 H)，7.67-7.76(m，1 H)，7.84(s，2 H)，8.70(s，2 H)，9.35(s，1 H)，9.67(s，1 H)。 TLC: Rf 0.32 (chloroform:methanol = 10:1); 1 H-NMR (DMSO-d 6 ): δ 1.17 (t, 3 H), 3.20-3.33 (m, 2 H), 7.14 (d, 2 H) ), 7.38-7.49 (m, 4 H), 7.67-7.76 (m, 1 H), 7.84 (s, 2 H), 8.70 (s, 2 H), 9.35 (s, 1 H), 9.67 (s, 1 H).

實施例85-89：1-[2-(1H-咪唑-1-基)-5-(三氟甲基)苯基]-3-[2-({6-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]-3-吡啶基}氧基)-5-嘧啶基]脲 Example 85-89: 1-[2-(1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl]-3-[2-({6-[2-(2-)-oxygen -ylpyrrolidinyl)-1,3-thiazol-5-yl]-3-pyridyl}oxy)-5-pyrimidinyl]urea

TLC：Rf 0.44(乙酸乙酯：甲醇=9：1)；1H-NMR(DMSO-d6)：δ 2.15(quint，2 H)，2.63(t，2 H)，4.05(t，2 H)，7.18(s，1 H)，7.46-7.56(m，3 H)，7.72-7.77(m，1 H)，7.96(s，1 H)，8.01(d，1 H)，8.17(s，1 H)，8.32(s，1 H)，8.43-8.47(m，1 H)，8.48(s，1 H)，8.67(s，2 H)，9.44(s，1 H)。 TLC: Rf 0.44 (ethyl acetate: methanol = 9: 1); 1 H -NMR (DMSO-d 6): δ 2.15 (quint, 2 H), 2.63 (t, 2 H), 4.05 (t, 2 H ), 7.18 (s, 1 H), 7.46-7.56 (m, 3 H), 7.72-7.77 (m, 1 H), 7.96 (s, 1 H), 8.01 (d, 1 H), 8.17 (s, 1 H), 8.32 (s, 1 H), 8.43 - 8.47 (m, 1 H), 8.48 (s, 1 H), 8.67 (s, 2 H), 9.44 (s, 1 H).

實施例85-90：1-(2-{4-[2-(二甲胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-(3-吡啶基)-5-(三氟甲基)苯基]脲 Example 85-90: 1-(2-{4-[2-(Dimethylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-[2- (3-pyridyl)-5-(trifluoromethyl)phenyl]urea

TLC：Rf 0.30(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 3.08(s，6 H)，7.14(d，2 H)，7.46-7.60(m，6 H)，7.87-7.93(m，1 H)，8.34(s，1 H)，8.36(s，1 H)，8.61-8.74(m，4 H)，9.34(s，1 H)。 TLC: Rf 0.30 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 3.08 (s, 6 H), 7.14 (d, 2 H), 7.46 - 7.60 (m, 6 H), 7.87- 7.93 (m, 1 H), 8.34 (s, 1 H), 8.36 (s, 1 H), 8.61 - 8.74 (m, 4 H), 9.34 (s, 1 H).

實施例85-91：1-[2-(3-吡啶基)-5-(三氟甲基)苯基]-3-[2-(4-{2-[(四氫-2H-吡喃-4-基甲基)胺基]-1，3-噻唑-5-基}苯氧基)-5-嘧啶基]脲 Example 85-91:1-[2-(3-Pyridinyl)-5-(trifluoromethyl)phenyl]-3-[2-(4-{2-[(tetrahydro-2H-pyran) -4-ylmethyl)amino]-1,3-thiazol-5-yl}phenoxy)-5-pyrimidinyl]urea

TLC：Rf 0.30(乙酸乙酯)； 1H-NMR(DMSO-d6)：δ 1.14-1.23(m，2 H)，1.62(d，2 H)，1.84(m，1 H)，3.13(t，2 H)，3.21-3.30(m，2 H)，3.85(dd，2 H)，7.12(d，2 H)，7.38-7.60(m，6 H)，7.82(t，1 H)，7.86-7.92(m，1 H)，8.22(s，1 H)，8.37(s，1 H)，8.60-8.70(m，4 H)，9.21(s，1 H)。 TLC: Rf 0.30 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 1.14-1.23 (m, 2 H), 1.62 (d, 2 H), 1.84 (m, 1 H), 3.13 ( t, 2 H), 3.21-3.30 (m, 2 H), 3.85 (dd, 2 H), 7.12 (d, 2 H), 7.38-7.60 (m, 6 H), 7.82 (t, 1 H), 7.86-7.92 (m, 1 H), 8.22 (s, 1 H), 8.37 (s, 1 H), 8.60-8.70 (m, 4 H), 9.21. (s, 1 H).

實施例85-92：1-(2-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-(1H-咪唑-1-基)-5-(三氟甲基)苯基]脲 Example 85-92: 1-(2-{4-[2-(ethylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-[2-( 1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl]urea

TLC：Rf 0.60(乙酸乙酯：甲醇=9：1)；1H-NMR(DMSO-d6)：δ 1.16(t，3 H)，3.24(q，2 H)，7.10(s，1 H)，7.11(d，2 H)，7.39-7.56(m，6 H)，7.72(br s，1 H)，7.96(s，1 H)，8.29(s，1 H)，8.42(s，1 H)，8.65(s，2 H)，10.0(br s，1 H)。 TLC: Rf 0.60 (ethyl acetate:methanol = 9:1); 1 H-NMR (DMSO-d 6 ): δ 1.16 (t, 3 H), 3.24 (q, 2 H), 7.10 (s, 1 H) ), 7.11 (d, 2 H), 7.39-7.56 (m, 6 H), 7.72 (br s, 1 H), 7.96 (s, 1 H), 8.29 (s, 1 H), 8.42 (s, 1) H), 8.65 (s, 2 H), 10.0 (br s, 1 H).

實施例85-93：1-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-(4H-1，2，4-三唑-4-基)-5-(三氟甲基)苯基]脲 Example 85-93: 1-(2-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl )-3-[2-(4H-1,2,4-triazol-4-yl)-5-(trifluoromethyl)phenyl]urea

TLC：Rf 0.40(乙酸乙酯)；1H-NMR(CDCl3)：δ 2.30(m，2 H)，2.74(t，2 H)，4.20(t，2 H)，7.23(d，2 H)，7.59-7.77(m，5 H)，7.91(d，1 H)，8.16(s，1 H)，8.44(s，1 H)，8.54(s，1 H)，8.80(s，2 H)，9.42(s，1 H)。 TLC: Rf 0.40 (ethyl acetate); 1 H-NMR (CDCl 3 ): δ 2.30 (m, 2 H), 2.74 (t, 2 H), 4.20 (t, 2 H), 7.23 (d, 2 H) ), 7.59-7.77 (m, 5 H), 7.91 (d, 1 H), 8.16 (s, 1 H), 8.44 (s, 1 H), 8.54 (s, 1 H), 8.80 (s, 2 H) ), 9.42 (s, 1 H).

實施例85-94：1-(6-{4-[2-(二甲胺基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)-3-[3-(三氟甲基)苯基]脲 Example 85-94: 1-(6-{4-[2-(Dimethylamino)-1,3-thiazol-5-yl]phenoxy}-3-pyridyl)-3-[3- (trifluoromethyl)phenyl]urea

TLC：Rf 0.28(己烷：乙酸乙酯=1：2)；1H-NMR(DMSO-d6)：δ 3.06(s，6 H)，6.99-7.08(m，3 H)，7.30(d，1 H)，7.44-7.64(m，5 H)，7.97-8.01(m，2 H)，8.18(d，1 H)，8.87(s，1 H)，9.12(s，1 H)。 TLC: Rf 0.28 (hexane: ethyl acetate = 1:2); 1 H-NMR (DMSO-d 6 ): δ 3.06 (s, 6 H), 6.99-7.08 (m, 3 H), 7.30 (d) , 1 H), 7.44-7.64 (m, 5 H), 7.97-8.01 (m, 2 H), 8.18 (d, 1 H), 8.87 (s, 1 H), 9.12 (s, 1 H).

實施例85-95：1-(2-{4-[2-(二乙胺基)-1，3-噻唑-5-基]苯氧 基}-5-嘧啶基)-3-[3-(三氟甲基)苯基]脲 Example 85-95: 1-(2-{4-[2-(Diethylamino)-1,3-thiazol-5-yl]phenoxy }-5-pyrimidinyl)-3-[3-(trifluoromethyl)phenyl]urea

TLC：Rf 0.22(氯仿：甲醇=19：1)；1H-NMR(DMSO-d6)：δ 1.18(t，6 H)，3.47(q，4 H)，7.12-7.18(m，2 H)，7.30-7.35(m，1 H)，7.45-7.54(m，4 H)，7.59-7.64(m，1 H)，7.95-7.99(m，1 H)，8.71(s，2 H)，8.97(s，1 H)，9.31(s，1 H)。 TLC: Rf 0.22 (chloroform:methanol = 19:1); 1 H-NMR (DMSO-d 6 ): δ 1.18 (t, 6 H), 3.47 (q, 4 H), 7.12-7.18 (m, 2 H) ), 7.30-7.35 (m, 1 H), 7.45-7.54 (m, 4 H), 7.59-7.64 (m, 1 H), 7.95-7.99 (m, 1 H), 8.71 (s, 2 H), 8.97 (s, 1 H), 9.31 (s, 1 H).

實施例85-96：1-(6-{4-[2-(二甲胺基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)-3-[2-(3-吡啶基)-5-(三氟甲基)苯基]脲 Example 85-96: 1-(6-{4-[2-(Dimethylamino)-1,3-thiazol-5-yl]phenoxy}-3-pyridyl)-3-[2- (3-pyridyl)-5-(trifluoromethyl)phenyl]urea

TLC：Rf 0.61(乙酸乙酯：甲醇=9：1)；1H-NMR(DMSO-d6)：δ 3.06(s，6 H)，6.98(d，1 H)，7.02-7.06(m，2 H)，7.42-7.48(m，4 H)，7.51(s，1 H)，7.53-7.58(m，1 H)，7.86-7.90(m，1 H)，7.96(dd，1 H)，8.06-8.07(m，2 H)，8.41(s，1 H)，8.63-8.68(m，2 H)，9.15(s，1 H)。 TLC: Rf 0.61 (ethyl acetate:methanol = 9:1); 1 H-NMR (DMSO-d 6 ): δ 3.06 (s, 6 H), 6.98 (d, 1 H), 7.02-7.06 (m, 2 H), 7.42-7.48 (m, 4 H), 7.51 (s, 1 H), 7.53-7.58 (m, 1 H), 7.86-7.90 (m, 1 H), 7.96 (dd, 1 H), 8.06-8.07 (m, 2 H), 8.41 (s, 1 H), 8.63-8.68 (m, 2 H), 9.15 (s, 1 H).

實施例85-97：1-[2-(4-{2-[3-(羥基甲基)-1-吡咯啶基]-1，3-噻唑-5-基}苯氧基)-5-嘧啶基]-3-[3-(三氟甲基)苯基]脲 Example 85-97: 1-[2-(4-{2-[3-(Hydroxymethyl)-1-pyrrolidinyl]-1,3-thiazol-5-yl}phenoxy)-5- Pyrimidinyl]-3-[3-(trifluoromethyl)phenyl]urea

TLC：Rf 0.31(乙酸乙酯：甲醇=9：1)；1H-NMR(DMSO-d6)：δ 1.48(m，1 H)，1.93(m，1 H)，2.11(br s，1 H)，3.32-3.50(m，3 H)，3.58-3.79(m，2 H)，4.03(dd，1 H)，4.80(s，1 H)，7.17(d，1 H)，7.24(s，1 H)，7.30(d，2 H)，7.32(d，1 H)，7.50(t，2 H)，7.62(d，1 H)，7.98(s，1 H)，8.72(s，2 H)，9.43(s，1 H)，9.70(s，1 H)。 TLC: Rf 0.31 (ethyl acetate:methanol = 9:1); 1 H-NMR (DMSO-d 6 ): δ 1.48 (m, 1 H), 1.93 (m, 1 H), 2.11 (br s, 1) H), 3.32-3.50 (m, 3 H), 3.58-3.79 (m, 2 H), 4.03 (dd, 1 H), 4.80 (s, 1 H), 7.17 (d, 1 H), 7.24 (s) , 1 H), 7.30 (d, 2 H), 7.32 (d, 1 H), 7.50 (t, 2 H), 7.62 (d, 1 H), 7.98 (s, 1 H), 8.72 (s, 2) H), 9.43 (s, 1 H), 9.70 (s, 1 H).

實施例85-98：1-(2-{4-[2-(甲胺基)-1，3-噻唑-5-基]苯氧 基}-5-嘧啶基)-3-[3-(三氟甲基)苯基]脲 Example 85-98: 1-(2-{4-[2-(methylamino)-1,3-thiazol-5-yl]phenoxy }-5-pyrimidinyl)-3-[3-(trifluoromethyl)phenyl]urea

TLC：Rf 0.51(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 2.84(d，3 H)，7.14(d，2 H)，7.32(d，1 H)，7.45(d，1 H)，7.50(d，2 H)，7.50-7.67(m，3 H)，7.97(s，1 H)，8.70(s，2 H)，8.97(s，1 H)，9.31(s，1 H)。 TLC: Rf 0.51 (ethyl acetate); 1 H-NMR (DMSO -d 6): δ 2.84 (d, 3 H), 7.14 (d, 2 H), 7.32 (d, 1 H), 7.45 (d, 1 H), 7.50 (d, 2 H), 7.50-7.67 (m, 3 H), 7.97 (s, 1 H), 8.70 (s, 2 H), 8.97 (s, 1 H), 9.31 (s, 1 H).

實施例85-99：1-(2-{4-[2-(異丙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[3-(三氟甲基)苯基]脲 Examples 85-99: 1-(2-{4-[2-(Isopropylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-[3-( Trifluoromethyl)phenyl]urea

TLC：Rf 0.69(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 1.18(d，6 H)，3.80(m，1 H)，7.14(d，2 H)，7.32(d，1 H)，7.41(s，1 H)，7.45(d，2 H)，7.51(t，1 H)，7.61(s，1 H)，7.66(d，1 H)，7.97(s，1 H)，8.70(s，1 H)，8.96(s，1 H)，9.30(s，1 H)。 TLC: Rf 0.69 (ethyl acetate); 1 H-NMR (DMSO -d 6): δ 1.18 (d, 6 H), 3.80 (m, 1 H), 7.14 (d, 2 H), 7.32 (d, 1 H), 7.41 (s, 1 H), 7.45 (d, 2 H), 7.51 (t, 1 H), 7.61 (s, 1 H), 7.66 (d, 1 H), 7.97 (s, 1 H) ), 8.70 (s, 1 H), 8.96 (s, 1 H), 9.30 (s, 1 H).

實施例85-100：1-(2-{4-[2-(異丁胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[3-(三氟甲基)苯基]脲 Example 85-100: 1-(2-{4-[2-(isobutylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-[3- (trifluoromethyl)phenyl]urea

TLC：Rf 0.75(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 0.90(d，6 H)，1.88(m，1 H)，3.06(t，2 H)，7.14(d，2 H)，7.32(d，1 H)，7.41(s，1 H)，7.45(d，2 H)，7.51(t，1 H)，7.61(d，1 H)，7.80(t，1 H)，7.97(s，1 H)，8.70(s，1 H)，8.97(s，1 H)，9.30(s，1 H)。 TLC: Rf 0.75 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 0.90 (d, 6 H), 1.88 (m, 1 H), 3.06 (t, 2 H), 7.14 (d, 2 H), 7.32 (d, 1 H), 7.41 (s, 1 H), 7.45 (d, 2 H), 7.51 (t, 1 H), 7.61 (d, 1 H), 7.80 (t, 1 H) ), 7.97 (s, 1 H), 8.70 (s, 1 H), 8.97 (s, 1 H), 9.30 (s, 1 H).

實施例85-101：1-(3-氯苯基)-3-(2-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 85-101:1-(3-Chlorophenyl)-3-(2-{4-[2-(ethylamino)-1,3-thiazol-5-yl]phenoxy}-5- Pyrimidinyl urea

TLC：Rf 0.80(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 1.17(t，3 H)，3.21-3.34(m，2 H)，7.00-7.07(m，1 H)，7.11-7.17(m，2 H)，7.27-7.33(m，2 H)，7.41-7.48(m， 3 H)，7.65-7.75(m，2 H)，8.69(s，2 H)，9.05(s，1 H)，9.25(s，1 H)。 TLC: Rf 0.80 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 1.17 (t, 3 H), 3.21-3.34 (m, 2 H), 7.00-7.07 (m, 1 H), 7.11-7.17 (m, 2 H), 7.27-7.33 (m, 2 H), 7.41-7.48 (m, 3 H), 7.65-7.75 (m, 2 H), 8.69 (s, 2 H), 9.05 ( s, 1 H), 9.25 (s, 1 H).

實施例85-102：1-(2，5-二氯苯基)-3-(2-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 85-102: 1-(2,5-Dichlorophenyl)-3-(2-{4-[2-(ethylamino)-1,3-thiazol-5-yl]phenoxy} -5-pyrimidinyl)urea

TLC：Rf 0.76(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 1.17(t，3 H)，3.21-3.34(m，2 H)，7.10-7.18(m，3 H)，7.42-7.52(m，4 H)，7.72(t，1 H)，8.25(d，1 H)，8.65(s，1 H)，8.71(s，2 H)，9.69(s，1 H)。 TLC: Rf 0.76 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 1.17 (t, 3 H), 3.21-3.34 (m, 2 H), 7.10-7.18 (m, 3 H), 7.42-7.52 (m, 4 H), 7.72 (t, 1 H), 8.25 (d, 1 H), 8.65 (s, 1 H), 8.71 (s, 2 H), 9.69 (s, 1 H).

實施例85-103：1-[2-氯-5-(三氟甲基)苯基]-3-(2-{4-[2-(二甲胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 85-103: 1-[2-Chloro-5-(trifluoromethyl)phenyl]-3-(2-{4-[2-(dimethylamino)-1,3-thiazole-5 -yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.30(己烷：乙酸乙酯=1：2)；1H-NMR(DMSO-d6)：δ 3.07(s，6 H)，7.16(d，2 H)，7.39(dd，1 H)，7.49(d，2 H)，7.55(s，1 H)，7.72(d，1 H)，8.56(d，1 H)，8.72(s，2 H)，8.77(s，1 H)，9.69(s，1 H)。 TLC: Rf 0.30 (hexane: ethyl acetate = 1: 2); 1 H -NMR (DMSO-d 6): δ 3.07 (s, 6 H), 7.16 (d, 2 H), 7.39 (dd, 1 H), 7.49 (d, 2 H), 7.55 (s, 1 H), 7.72 (d, 1 H), 8.56 (d, 1 H), 8.72 (s, 2 H), 8.77 (s, 1 H) , 9.69 (s, 1 H).

實施例85-104：1-{2-[4-(2-胺基-1，3-噻唑-5-基)苯氧基]-5-嘧啶基}-3-[2-(3-吡啶基)-5-(三氟甲基)苯基]脲 Example 85-104: 1-{2-[4-(2-Amino-1,3-thiazol-5-yl)phenoxy]-5-pyrimidinyl}-3-[2-(3-pyridine 5-(3-trifluoromethyl)phenyl]urea

TLC：Rf 0.66(乙酸乙酯：甲醇=9：1)； 1H-NMR(CDCl3)：δ 7.10-7.14(m，2 H)，7.23(s，1 H)，7.45-7.62(m，5 H)，7.93-7.97(m，1 H)，8.54(s，1 H)，8.60-8.63(m，4 H)。 TLC: Rf 0.66 (ethyl acetate:methanol = 9:1); 1 H-NMR (CDCl 3 ): δ 7.10-7.14 (m, 2 H), 7.23 (s, 1 H), 7.45-7.62 (m, 5 H), 7.93-7.97 (m, 1 H), 8.54 (s, 1 H), 8.60-8.63 (m, 4 H).

實施例85-105：1-[2-(4-{2-[(環丙基甲基)胺基]-1，3-噻唑-5-基}苯氧基)-5-嘧啶基]-3-[3-(三氟甲基)苯基]脲 Example 85-105: 1-[2-(4-{2-[(cyclopropylmethyl)amino]-1,3-thiazol-5-yl}phenoxy)-5-pyrimidinyl]- 3-[3-(trifluoromethyl)phenyl]urea

TLC：Rf 0.79(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 0.22(q，2 H)，0.46(q，2 H)，1.07(m，1 H)，3.13(t，2 H)，7.14(d，2 H)，7.32(d，1 H)，7.41(s，1 H)，7.45(d，2 H)，7.50(t，1 H)，7.61(d，1 H)，7.84(t，1 H)，7.96(s，1 H)，8.69(s，2 H)，8.95(s，1 H)，9.29(s，1 H)。 TLC: Rf 0.79 (ethyl acetate); 1 H-NMR (DMSO -d 6): δ 0.22 (q, 2 H), 0.46 (q, 2 H), 1.07 (m, 1 H), 3.13 (t, 2 H), 7.14 (d, 2 H), 7.32 (d, 1 H), 7.41 (s, 1 H), 7.45 (d, 2 H), 7.50 (t, 1 H), 7.61 (d, 1 H) ), 7.84 (t, 1 H), 7.96 (s, 1 H), 8.69 (s, 2 H), 8.95 (s, 1 H), 9.29 (s, 1 H).

實施例85-106：1-(2-{4-[2-(環丁基胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[3-(三氟甲基)苯基]脲 Examples 85-106: 1-(2-{4-[2-(Cyclobutylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-[3 -(trifluoromethyl)phenyl]urea

TLC：Rf 0.79(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 1.68(m，2 H)，1.94(m，2 H)，2.31(m，2 H)，4.06(m，1 H)，7.14(d，2 H)，7.32(d，1 H)，7.42(s，1 H)，7.45(d，2 H)，7.50(t，1 H)，7.61(d，1 H)，7.96(s，1 H)，8.03(d，1 H)，8.69(s，2 H)，8.96(s，1 H)，9.29(s，1 H)。 TLC: Rf 0.79 (ethyl acetate); 1 H-NMR (DMSO -d 6): δ 1.68 (m, 2 H), 1.94 (m, 2 H), 2.31 (m, 2 H), 4.06 (m, 1 H), 7.14 (d, 2 H), 7.32 (d, 1 H), 7.42 (s, 1 H), 7.45 (d, 2 H), 7.50 (t, 1 H), 7.61 (d, 1 H) ), 7.96 (s, 1 H), 8.03 (d, 1 H), 8.69 (s, 2 H), 8.96 (s, 1 H), 9.29 (s, 1 H).

實施例85-107：1-(2-{4-[2-(環戊胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[3-(三氟甲基)苯基]脲 Example 85-107: 1-(2-{4-[2-(Cyclopentylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-[3- (trifluoromethyl)phenyl]urea

TLC：Rf 0.79(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 1.52(m，4 H)，1.67(m，2 H)，1.93(m，2 H)，3.94(m，1 H)，4.06(m，1 H)，7.14(d，2 H)，7.32(d，1 H)，7.42 (s，1 H)，7.45(d，2 H)，7.50(t，1 H)，7.61(d，1 H)，7.76(d，1 H)，7.96(s，1 H)，8.70(s，2 H)，8.95(s，1 H)，9.29(s，1 H)。 TLC: Rf 0.79 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 1.52 (m, 4 H), 1.67 (m, 2 H), 1.93 (m, 2 H), 3.94 (m, 1 H), 4.06 (m, 1 H), 7.14 (d, 2 H), 7.32 (d, 1 H), 7.42 (s, 1 H), 7.45 (d, 2 H), 7.50 (t, 1 H) ), 7.61 (d, 1 H), 7.76 (d, 1 H), 7.96 (s, 1 H), 8.70 (s, 2 H), 8.95 (s, 1 H), 9.29 (s, 1 H).

實施例85-108：1-[2-氯-4-(三氟甲基)苯基]-3-(6-{4-[2-(二甲胺基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)脲 Example 85-108: 1-[2-Chloro-4-(trifluoromethyl)phenyl]-3-(6-{4-[2-(dimethylamino)-1,3-thiazole-5 -yl]phenoxy}-3-pyridyl)urea

TLC：Rf 0.48(己烷：乙酸乙酯=1：2)；1H-NMR(DMSO-d6)：δ 3.06(s，6 H)，7.03(s，1 H)，7.05-7.10(m，2 H)，7.45-7.49(m，2 H)，7.53(s，1 H)，7.68(dd，1 H)，7.87(d，1 H)，8.02(dd，1 H)，8.20(d，1 H)，8.44(d，1 H)，8.67(s，1 H)，9.68(s，1 H)。 TLC: Rf 0.48 (hexane: ethyl acetate = 1: 2); 1 H -NMR (DMSO-d 6): δ 3.06 (s, 6 H), 7.03 (s, 1 H), 7.05-7.10 (m , 2 H), 7.45-7.49 (m, 2 H), 7.53 (s, 1 H), 7.68 (dd, 1 H), 7.87 (d, 1 H), 8.02 (dd, 1 H), 8.20 (d) , 1 H), 8.44 (d, 1 H), 8.67 (s, 1 H), 9.68 (s, 1 H).

實施例85-109：1-(6-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)-3-[2-氟-5-(三氟甲基)苯基]脲 Example 85-109: 1-(6-{4-[2-(ethylamino)-1,3-thiazol-5-yl]phenoxy}-3-pyridyl)-3-[2-fluoro -5-(trifluoromethyl)phenyl]urea

TLC：Rf 0.60(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 1.16(t，3 H)，3.23-3.27(m，2 H)，7.00-7.07(m，3 H)，7.36-7.39(m，5 H)，7.66-7.76(m，1 H)，8.03(dd，1 H)，8.17(d，1 H)，8.56(d，1 H)，8.97(s，1 H)，9.25(s，1 H)。 TLC: Rf 0.60 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 1.16 (t, 3 H), 3.23 - 3.27 (m, 2 H), 7.00 - 7.07 (m, 3 H), 7.36-7.39 (m, 5 H), 7.66-7.76 (m, 1 H), 8.03 (dd, 1 H), 8.17 (d, 1 H), 8.56 (d, 1 H), 8.97 (s, 1 H) ), 9.25 (s, 1 H).

實施例85-110：1-[2-氯-5-(三氟甲基)苯基]-3-(6-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)脲 Example 85-110: 1-[2-Chloro-5-(trifluoromethyl)phenyl]-3-(6-{4-[2-(ethylamino)-1,3-thiazole-5- Phenoxy}-3-pyridyl)urea

TLC：Rf 0.62(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 1.16(t，3 H)，3.21-3.27(m，2 H)，7.01-7.08(m，3 H)，7.36-7.45(m，4 H)，7.68-7.73(m，2 H)，8.04(dd，1 H)，8.17(d，1 H)，8.60(s，1 H)，8.66(s，1 H)，9.63(s，1 H)。 TLC: Rf 0.62 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 1.16 (t, 3 H), 3.21-3.27 (m, 2 H), 7.01-7.08 (m, 3 H), 7.36-7.45 (m, 4 H), 7.68-7.73 (m, 2 H), 8.04 (dd, 1 H), 8.17 (d, 1 H), 8.60 (s, 1 H), 8.66 (s, 1 H) ), 9.63 (s, 1 H).

實施例85-111：1-[2-氯-4-(三氟甲基)苯基]-3-(6-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)脲 Example 85-111:1-[2-Chloro-4-(trifluoromethyl)phenyl]-3-(6-{4-[2-(ethylamino)-1,3-thiazole-5- Phenoxy}-3-pyridyl)urea

TLC：Rf 0.64(乙酸乙酯)； 1H-NMR(DMSO-d6)：δ 1.16(t，3 H)，3.21-3.27(m，2 H)，7.02-7.08(m，3 H)，7.40-7.44(m，3 H)，7.66-7.71(m，2 H)，7.87(s，1 H)，8.02(d，1 H)，8.19(d，1 H)，8.45(d，1 H)，8.67(s，1 H)，9.68(s，1 H)。 TLC: Rf 0.64 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 1.16 (t, 3 H), 3.21-3.27 (m, 2 H), 7.02-7.08 (m, 3 H), 7.40-7.44 (m, 3 H), 7.66-7.71 (m, 2 H), 7.87 (s, 1 H), 8.02 (d, 1 H), 8.19 (d, 1 H), 8.45 (d, 1 H) ), 8.67 (s, 1 H), 9.68 (s, 1 H).

實施例85-112：1-(2-{4-[2-(四氫-3-呋喃基胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[3-(三氟甲基)苯基]脲 Example 85-112: 1-(2-{4-[2-(tetrahydro-3-furylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)- 3-[3-(trifluoromethyl)phenyl]urea

TLC：Rf 0.22(氯仿：甲醇=9：1)；1H-NMR(DMSO-d6)：δ 1.79-1.90(m，1 H)，2.11-2.24(m，1 H)，3.61(dd，1 H)，3.67-3.86(m，3 H)，4.21-4.31(m，1 H)，7.12-7.18(m，2 H)，7.30-7.35(m，1 H)，7.43-7.54(m，4 H)，7.58-7.64(m，1 H)，7.95-8.01(m，2 H)，8.70(s，2 H)，8.98(s，1 H)，9.31(s，1 H)。 TLC: Rf 0.22 (chloroform:methanol = 9:1); 1 H-NMR (DMSO-d 6 ): δ 1.79-1.90 (m, 1 H), 2.11-2.24 (m, 1 H), 3.61 (dd, 1 H), 3.67-3.86 (m, 3 H), 4.21-4.31 (m, 1 H), 7.12-7.18 (m, 2 H), 7.30-7.35 (m, 1 H), 7.43-7.54 (m, 4 H), 7.58-7.64 (m, 1 H), 7.95-8.01 (m, 2 H), 8.70 (s, 2 H), 8.98 (s, 1 H), 9.31 (s, 1 H).

實施例85-113：1-(2-{4-[2-(3-氧雜環丁烷基胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[3-(三氟甲基)苯基]脲 Examples 85-113: 1-(2-{4-[2-(3-oxetanylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl) -3-[3-(trifluoromethyl)phenyl]urea

TLC：Rf 0.17(氯仿：甲醇=9：1)；1H-NMR(DMSO-d6)：δ 3.36-3.56(m，2 H)，3.70(dd，1 H)，3.91(t，1 H)，4.34-4.45(m，1 H)，4.78(t，1 H)，7.13-7.19(m，2 H)，7.30-7.38(m，3 H)，7.47-7.55(m，2 H)，7.58-7.64(m，1 H)，7.95-8.00(m，1 H)，8.70(s，2 H)，8.98(s，1 H)，9.31(s，1 H)。 TLC: Rf 0.17 (chloroform:methanol = 9:1); 1 H-NMR (DMSO-d 6 ): δ 3.36-3.56 (m, 2 H), 3.70 (dd, 1 H), 3.91 (t, 1 H) ), 4.34 - 4.45 (m, 1 H), 4.78 (t, 1 H), 7.13-7.19 (m, 2 H), 7.30-7.38 (m, 3 H), 7.47-7.55 (m, 2 H), 7.58-7.64 (m, 1 H), 7.95-8.00 (m, 1 H), 8.70 (s, 2 H), 8.98 (s, 1 H), 9.31 (s, 1 H).

實施例85-114：1-[6’-甲基-5-(三氟甲基)-2，3’-二吡啶-3-基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5- 嘧啶基)脲 Example 85-114: 1-[6'-Methyl-5-(trifluoromethyl)-2,3'-dipyridin-3-yl]-3-(2-{4-[2-(2) -Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5- Pyrimidinyl urea

TLC：Rf 0.58(乙酸乙酯：甲醇=9：1)；1H-NMR(DMSO-d6)：δ 2.10-2.23(m，2 H)，2.57(s，3 H)，2.64(t，2 H)，4.05(t，2 H)，7.21(d，2 H)，7.44(d，1 H)，7.67(d，2 H)，7.89(s，1 H)，7.95(dd，1 H)，8.54(s，1 H)，8.67(s，2 H)，8.71(dd，1 H)，8.75(s，2 H)，9.35(s，1 H)。 TLC: Rf 0.58 (ethyl acetate:methanol = 9:1); 1 H-NMR (DMSO-d 6 ): δ 2.10-2.23 (m, 2 H), 2.57 (s, 3 H), 2.64 (t, 2 H), 4.05 (t, 2 H), 7.21 (d, 2 H), 7.44 (d, 1 H), 7.67 (d, 2 H), 7.89 (s, 1 H), 7.95 (dd, 1 H) ), 8.54 (s, 1 H), 8.67 (s, 2 H), 8.71 (dd, 1 H), 8.75 (s, 2 H), 9.35 (s, 1 H).

實施例85-115：1-(2-{4-[2-(二丙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[3-(三氟甲基)苯基]脲 Example 85-115: 1-(2-{4-[2-(Dipropylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-[3-( Trifluoromethyl)phenyl]urea

TLC：Rf 0.80(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 0.89(t，6 H)，1.55-1.75(m，4 H)，3.25-3.50(m，4 H)，7.14(d，2 H)，7.32(d，1 H)，7.46(d，2 H)，7.49(s，1 H)，7.50(t，1 H)，7.59(d，1 H)，7.96(s，1 H)，8.70(s，2 H)，8.95(s，1 H)，9.29(s，1 H)。 TLC: Rf 0.80 (ethyl acetate); 1 H-NMR (DMSO -d 6): δ 0.89 (t, 6 H), 1.55-1.75 (m, 4 H), 3.25-3.50 (m, 4 H), 7.14 (d, 2 H), 7.32 (d, 1 H), 7.46 (d, 2 H), 7.49 (s, 1 H), 7.50 (t, 1 H), 7.59 (d, 1 H), 7.96 ( s, 1 H), 8.70 (s, 2 H), 8.95 (s, 1 H), 9.29 (s, 1 H).

實施例85-116：1-{2-[4-(2-{[2-(3-氧雜環丁烷基)乙基]胺基}-1，3-噻唑-5-基)苯氧基]-5-嘧啶基}-3-[3-(三氟甲基)苯基]脲 Examples 85-116: 1-{2-[4-(2-{[2-(3-oxetanyl)ethyl]amino}-1,3-thiazol-5-yl)phenoxy 5-[3-(trifluoromethyl)phenyl]urea

TLC：Rf 0.33(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 1.92(q，2 H)，2.95-3.10(m，1 H)，3.19(q，2 H)，4.27(t，2 H)，4.64(dd，2 H)，7.14(dd，2 H)，7.32(d，1 H)，7.43(s，1 H)，7.45(d，2 H)，7.51(t，1 H)，7.62(d，1 H)，7.73(t，1 H)，7.97(s，1 H)，8.70(s，2 H)，8.96(s，1 H)，9.30(s，1 H)。 TLC: Rf 0.33 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 1.92 (q, 2 H), 2.95-3.10 (m, 1 H), 3.19 (q, 2 H), 4.27 ( t,2 H), 4.64 (dd, 2 H), 7.14 (dd, 2 H), 7.32 (d, 1 H), 7.43 (s, 1 H), 7.45 (d, 2 H), 7.51 (t, 1 H), 7.62 (d, 1 H), 7.73 (t, 1 H), 7.97 (s, 1 H), 8.70 (s, 2 H), 8.96 (s, 1 H), 9.30 (s, 1 H) ).

實施例85-117：1-[2-氯-5-(三氟甲基)苯基]-3-(2-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 85-117: 1-[2-Chloro-5-(trifluoromethyl)phenyl]-3-(2-{4-[2-(propylamino)-1,3-thiazol-5-yl Phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.56(乙酸乙酯：甲醇=9：1)；1H-NMR(DMSO-d6)：δ 0.91(t，3 H)，1.51-1.63(m，2 H)，3.15-3.23(m，2 H)，7.13-7.17(m，2 H)，7.38-7.48(m，4 H)，7.71-7.78(m，2 H)，8.56(d，1 H)，8.72(s，2 H)，8.77(s，1 H)，9.69(s，1 H)。 TLC: Rf 0.56 (ethyl acetate:methanol = 9:1); 1 H-NMR (DMSO-d 6 ): δ 0.91 (t, 3 H), 1.51-1.63 (m, 2 H), 3.15-3.23 ( m, 2 H), 7.13-7.17 (m, 2 H), 7.38-7.48 (m, 4 H), 7.71-7.78 (m, 2 H), 8.56 (d, 1 H), 8.72 (s, 2 H) ), 8.77 (s, 1 H), 9.69 (s, 1 H).

實施例85-118：1-[2-氯-4-(三氟甲基)苯基]-3-(2-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 85-118: 1-[2-Chloro-4-(trifluoromethyl)phenyl]-3-(2-{4-[2-(propylamino)-1,3-thiazol-5-yl Phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.73(乙酸乙酯：甲醇=9：1)；1H-NMR(DMSO-d6)：δ 0.91(t，3 H)，1.51-1.63(m，2 H)，3.16-3.23(m，2 H)，7.13-7.17(m，2 H)，7.42-7.48(m，3 H)，7.68(dd，1 H)，7.76(t，1 H)，7.88(d，1 H)，8.42(d，1 H)，8.72(s，2 H)，8.79(s，1 H)，9.75(s，1 H)。 TLC: Rf 0.73 (ethyl acetate:methanol = 9:1); 1 H-NMR (DMSO-d 6 ): δ 0.91 (t, 3 H), 1.51-1.63 (m, 2 H), 3.16-3.23 ( m, 2 H), 7.13-7.17 (m, 2 H), 7.42-7.48 (m, 3 H), 7.68 (dd, 1 H), 7.76 (t, 1 H), 7.88 (d, 1 H), 8.42 (d, 1 H), 8.72 (s, 2 H), 8.79 (s, 1 H), 9.75 (s, 1 H).

實施例85-119：1-[4-甲基-3-(三氟甲基)苯基]-3-(2-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 85-119: 1-[4-Methyl-3-(trifluoromethyl)phenyl]-3-(2-{4-[2-(propylamino)-1,3-thiazole-5- Phenyloxy-5-pyrimidinyl)urea

TLC：Rf 0.56(乙酸乙酯：甲醇=9：1)；1H-NMR(DMSO-d6)：δ 0.91(t，3 H)，1.51-1.63(m，2 H)，2.36(d，3 H)，3.16-3.23(m，2 H)，7.12-7.17(m，2 H)，7.33(d，1 H)，7.42-7.47(m，3 H)，7.53(dd，1 H)，7.76(t，1 H)，7.88(d，1 H)，8.69(s，2 H)，8.90(s，1 H)，9.17(s，1 H)。 TLC: Rf 0.56 (ethyl acetate: methanol = 9: 1); 1 H -NMR (DMSO-d 6): δ 0.91 (t, 3 H), 1.51-1.63 (m, 2 H), 2.36 (d, 3 H), 3.16-3.23 (m, 2 H), 7.12-7.17 (m, 2 H), 7.33 (d, 1 H), 7.42-7.47 (m, 3 H), 7.53 (dd, 1 H), 7.76 (t, 1 H), 7.88 (d, 1 H), 8.69 (s, 2 H), 8.90 (s, 1 H), 9.17 (s, 1 H).

實施例85-120：1-(2-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-(3-吡啶基)-5-(三氟甲基)苯基]脲 Example 85-120: 1-(2-{4-[2-(propylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-[2-(3 -pyridyl)-5-(trifluoromethyl)phenyl]urea

TLC：Rf 0.40(乙酸乙酯：甲醇=9：1)；1H-NMR(DMSO-d6)：δ 0.91(t，3 H)，1.51-1.63(m，2 H)，3.16-3.23(m，2 H)，7.10-7.15(m，2H)，7.41-7.57(m，6 H)，7.75(t，1 H)，7.87-7.91(m，1 H)，8.22(s，1 H)，8.38(s，1 H)，8.62-8.68(m，4 H)，9.22(s，1 H)。 TLC: Rf 0.40 (ethyl acetate:methanol = 9:1); 1 H-NMR (DMSO-d 6 ): δ 0.91 (t, 3 H), 1.51-1.63 (m, 2 H), 3.16-3. m,2 H), 7.10-7.15 (m, 2H), 7.41-7.57 (m, 6 H), 7.75 (t, 1 H), 7.87-7.91 (m, 1 H), 8.22 (s, 1 H) , 8.38 (s, 1 H), 8.62 - 8.68 (m, 4 H), 9.22 (s, 1 H).

實施例85-121：1-(6-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)-3-[2-(3-吡啶基)-5-(三氟甲基)苯基]脲 Example 85-121:1-(6-{4-[2-(propylamino)-1,3-thiazol-5-yl]phenoxy}-3-pyridyl)-3-[2-(3 -pyridyl)-5-(trifluoromethyl)phenyl]urea

TLC：Rf 0.10(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 0.91(t，3 H)，1.51-1.63(m，2 H)，3.16-3.21(m，2 H)，6.96-7.04(m，3 H)，7.38-7.60(m，6 H)，7.73(s，1 H)，7.92(d，1 H)，7.96(d，1 H)，8.09(d，1 H)，8.37-8.50(m，2 H)，8.63-8.66(m，2 H)，9.46(s，1 H)。 TLC: Rf 0.10 (ethyl acetate); 1 H-NMR (DMSO -d 6): δ 0.91 (t, 3 H), 1.51-1.63 (m, 2 H), 3.16-3.21 (m, 2 H), 6.96-7.04 (m, 3 H), 7.38-7.60 (m, 6 H), 7.73 (s, 1 H), 7.92 (d, 1 H), 7.96 (d, 1 H), 8.09 (d, 1 H) ), 8.37-8.50 (m, 2 H), 8.63 - 8.66 (m, 2 H), 9.46 (s, 1 H).

實施例85-122：1-(6-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)-3-[3-(三氟甲基)苯基]脲 Example 85-122: 1-(6-{4-[2-(propylamino)-1,3-thiazol-5-yl]phenoxy}-3-pyridyl)-3-[3-(three Fluoromethyl)phenyl]urea

TLC：Rf 0.48(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 0.91(t，3 H)，1.53-1.60(m，2 H)，3.16-3.22(m，2 H)，6.99-7.07(m，3 H)，7.28-7.57(m，6 H)，7.72-7.75(m，1 H)，7.98-8.01(m，2 H)，8.19(d，1 H)，8.91(s，1 H)，9.16(s，1 H)。 TLC: Rf 0.48 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 0.91 (t, 3 H), 1.53-1.60 (m, 2 H), 3.16-3.22 (m, 2 H), 6.99-7.07 (m, 3 H), 7.28-7.57 (m, 6 H), 7.72-7.75 (m, 1 H), 7.98-8.01 (m, 2 H), 8.19 (d, 1 H), 8.91 ( s, 1 H), 9.16 (s, 1 H).

實施例85-123：1-(2-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[5-(三氟甲基)-3-吡啶基]脲 Example 85-123: 1-(2-{4-[2-(ethylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-[5-( Trifluoromethyl)-3-pyridyl]urea

TLC：Rf 0.43(二氯甲烷：甲醇=9：1)；1H-NMR(DMSO-d6)：δ 1.17(t，3 H)，3.21-3.29(m，2 H)，7.12-7.17(m，2 H)，7.43-7.47(m，3 H)，7.72(t，1 H)，8.38(t，1 H)，8.58(d， 1 H)，8.71(s，2 H)，8.82(d，1 H)，9.18(s，1 H)，9.52(s，1 H)。 TLC: Rf 0.43 (dichloromethane:methanol = 9:1); 1 H-NMR (DMSO-d 6 ): δ 1.17 (t, 3 H), 3.21-3.29 (m, 2 H), 7.12. m, 2 H), 7.43-7.47 (m, 3 H), 7.72 (t, 1 H), 8.38 (t, 1 H), 8.58 (d, 1 H), 8.71 (s, 2 H), 8.82 ( d, 1 H), 9.18 (s, 1 H), 9.52 (s, 1 H).

實施例85-124：1-[2-(4-{2-[3-(2-羥基-2-丙基)-2-側氧基-1-吡咯啶基]-1，3-噻唑-5-基}苯氧基)-5-嘧啶基]-3-[2-苯基-5-(三氟甲基)-3-吡啶基]脲 Example 85-124: 1-[2-(4-{2-[3-(2-hydroxy-2-propyl)-2-oxo-l-pyrrolidinyl]-1,3-thiazole- 5-yl}phenoxy)-5-pyrimidinyl]-3-[2-phenyl-5-(trifluoromethyl)-3-pyridyl]urea

TLC：Rf 0.28(氯仿：甲醇=19：1)；1H-NMR(DMSO-d6)：δ 1.25(s，3 H)，1.28(s，3 H)，2.20-2.29(m，2 H)，2.78(t，1 H)，3.84-3.94(m，1 H)，3.98-4.08(m，1 H)，4.65(s，1 H)，7.20-7.26(m，2 H)，7.49-7.60(m，3 H)，7.64-7.70(m，4 H)，7.89(s，1 H)，8.42(s，1 H)，8.67(s，2 H)，8.71-8.78(m，2 H)，9.47(s，1 H)。 TLC: Rf 0.28 (chloroform:methanol = 19:1); 1 H-NMR (DMSO-d 6 ): δ 1.25 (s, 3 H), 1.28 (s, 3 H), 2.20-2.29 (m, 2 H) ), 2.78 (t, 1 H), 3.84-3.94 (m, 1 H), 3.98-4.08 (m, 1 H), 4.65 (s, 1 H), 7.20-7.26 (m, 2 H), 7.49- 7.60 (m, 3 H), 7.64-7.70 (m, 4 H), 7.89 (s, 1 H), 8.42 (s, 1 H), 8.67 (s, 2 H), 8.71-8.78 (m, 2 H) ), 9.47 (s, 1 H).

實施例85-125：1-(6-{4-[2-(1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)-3-[3-(三氟甲基)苯基]脲 Example 85-125: 1-(6-{4-[2-(1-Pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-3-pyridyl)-3-[3 -(trifluoromethyl)phenyl]urea

TLC：Rf 0.12(己烷：乙酸乙酯=1：1)；1H-NMR(DMSO-d6)：δ 1.96-2.00(m，4 H)，3.38-3.42(m，4 H)，7.00-7.07(m，3 H)，7.29-7.60(m，6 H)，7.98-8.01(m，2 H)，8.19(d，1 H)，8.88(s，1 H)，9.13(s，1 H)。 TLC: Rf 0.12 (hexane: ethyl acetate = 1:1); 1 H-NMR (DMSO-d 6 ): δ 1.96-2.00 (m, 4 H), 3.38-3.42 (m, 4 H), 7.00 -7.07 (m, 3 H), 7.29-7.60 (m, 6 H), 7.98-8.01 (m, 2 H), 8.19 (d, 1 H), 8.88 (s, 1 H), 9.13 (s, 1) H).

實施例85-126：1-(6-{4-[2-(1-哌啶基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)-3-[3-(三氟甲基)苯基]脲 Example 85-126: 1-(6-{4-[2-(1-piperidinyl)-1,3-thiazol-5-yl]phenoxy}-3-pyridyl)-3-[3 -(trifluoromethyl)phenyl]urea

TLC：Rf 0.46(己烷：乙酸乙酯=1：1)；1H-NMR(DMSO-d6)：δ 1.55-1.65(s，6 H)，3.44(s，4 H)，7.00-7.08(m，3 H)，7.30(d，1 H)，7.45-7.60(m，5 H)，7.98-8.02(m，2 H)，8.19(d，1 H)，8.88(s，1 H)，9.13(s，1 H)。 TLC: Rf 0.46 (hexane: ethyl acetate = 1: 1); 1 H -NMR (DMSO-d 6): δ 1.55-1.65 (s, 6 H), 3.44 (s, 4 H), 7.00-7.08 (m, 3 H), 7.30 (d, 1 H), 7.45-7.60 (m, 5 H), 7.98-8.02 (m, 2 H), 8.19 (d, 1 H), 8.88 (s, 1 H) , 9.13 (s, 1 H).

實施例85-127：1-[2-氯-5-(三氟甲基)-3-吡啶基]-3-(2-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 85-127: 1-[2-Chloro-5-(trifluoromethyl)-3-pyridyl]-3-(2-{4-[2-(ethylamino)-1,3-thiazole -5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.48(二氯甲烷：甲醇=9：1)；1H-NMR(DMSO-d6)：δ 1.16(t，3 H)，3.21-3.29(m，2 H)，7.15(d，2 H)，7.43-7.47(m，3 H)，7.72(t，1 H)，8.48(d，1 H)，8.73(s，2 H)，8.88(d，1 H)，8.95(s，1 H)，9.77(s，1 H)。 TLC: Rf 0.48 (dichloromethane:methanol = 9:1); 1 H-NMR (DMSO-d 6 ): δ 1.16 (t, 3 H), 3.21-3.29 (m, 2 H), 7.15 (d, 2 H), 7.43 - 7.47 (m, 3 H), 7.72 (t, 1 H), 8.48 (d, 1 H), 8.73 (s, 2 H), 8.88 (d, 1 H), 8.95 (s, 1 H), 9.77 (s, 1 H).

實施例85-128：1-[2-(4-{2-[乙基(甲基)胺基]-1，3-噻唑-5-基}苯氧基)-5-嘧啶基]-3-[3-(三氟甲基)苯基]脲 Example 85-128: 1-[2-(4-{2-[Ethyl(methyl)amino]-1,3-thiazol-5-yl}phenoxy)-5-pyrimidinyl]-3 -[3-(trifluoromethyl)phenyl]urea

TLC：Rf 0.32(己烷：乙酸乙酯=1：2)；1H-NMR(DMSO-d6)：δ 1.15(t，3 H)，3.03(s，3 H)，3.47-3.54(m，2 H)，7.13-7.17(m，2 H)，7.32(d，1 H)，7.46-7.53(m，4 H)，7.61(d，1 H)，7.96(s，1 H)，8.70(s，2 H)，8.96(s，1 H)，9.29(s，1 H)。 TLC: Rf 0.32 (hexane: ethyl acetate = 1: 2); 1 H -NMR (DMSO-d 6): δ 1.15 (t, 3 H), 3.03 (s, 3 H), 3.47-3.54 (m , 2 H), 7.13-7.17 (m, 2 H), 7.32 (d, 1 H), 7.46-7.53 (m, 4 H), 7.61 (d, 1 H), 7.96 (s, 1 H), 8.70 (s, 2 H), 8.96 (s, 1 H), 9.29 (s, 1 H).

實施例85-129：1-[2-(4-{2-[(2-甲氧基乙基)胺基]-1，3-噻唑-5-基}苯氧基)-5-嘧啶基]-3-[3-(三氟甲基)苯基]脲 Examples 85-129: 1-[2-(4-{2-[(2-Methoxyethyl)amino]-1,3-thiazol-5-yl}phenoxy)-5-pyrimidinyl ]-3-[3-(trifluoromethyl)phenyl]urea

TLC：Rf 0.58(二氯甲烷：甲醇=9：1)；1H-NMR(DMSO-d6)：δ 3.27(s，3 H)，3.41-3.51(m，4 H)，7.12-7.16(m，2 H)，7.32(d，1 H)，7.41-7.59(m，4 H)，7.61(d，1 H)，7.82(t，1 H)，7.96(s，1 H)，8.69(s，2 H)，8.95(s，1 H)，9.29(s，1 H)。 TLC: Rf 0.58 (dichloromethane:methanol = 9:1); 1 H-NMR (DMSO-d 6 ): δ 3.27 (s, 3 H), 3.41-3.51 (m, 4 H), 7.12. m, 2 H), 7.32 (d, 1 H), 7.41-7.59 (m, 4 H), 7.61 (d, 1 H), 7.82 (t, 1 H), 7.96 (s, 1 H), 8.69 ( s, 2 H), 8.95 (s, 1 H), 9.29 (s, 1 H).

實施例85-130：1-[5-氟-2-(3-吡啶基)苯基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 85-130: 1-[5-Fluoro-2-(3-pyridyl)phenyl]-3-(2-{4-[2-(2-o-oxy-1-pyrrolidinyl)- 1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.34(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 2.10-2.23(m，2 H)，2.64(t，2 H)，4.05(t，2 H)，7.01(dt，1 H)，7.21(d，2 H)，7.29(dd，1 H)，7.51(dd，1 H)，7.66(d，2 H)，7.80(m，3 H)，8.10(s，1 H)，8.55-8.68(m，4 H)，9.22(s，1 H)。 TLC: Rf 0.34 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 2.10-2.23 (m, 2 H), 2.64 (t, 2 H), 4.05 (t, 2 H), 7.01 ( Dt, 1 H), 7.21 (d, 2 H), 7.29 (dd, 1 H), 7.51 (dd, 1 H), 7.66 (d, 2 H), 7.80 (m, 3 H), 8.10 (s, 1 H), 8.55-8.68 (m, 4 H), 9.22 (s, 1 H).

實施例85-131：1-(3，5-二氟苯基)-3-(2-{4-[2-(乙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 85-131:1-(3,5-Difluorophenyl)-3-(2-{4-[2-(ethylamino)-1,3-thiazol-5-yl]phenoxy} -5-pyrimidinyl)urea

TLC：Rf 0.75(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 1.17(t，3 H)，3.22-3.30(m，2 H)，6.82(dt，1 H)，7.12-7.25(m，4 H)，7.42-7.47(m，3 H)，7.72(t，1 H)，8.69(s，2 H)，9.01(s，1 H)，9.35(s，1 H)。 TLC: Rf 0.75 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 1.17 (t, 3 H), 3.22-3.30 (m, 2 H), 6.82 (dt, 1 H), 7.12 7.25 (m, 4 H), 7.42-7.47 (m, 3 H), 7.72 (t, 1 H), 8.69 (s, 2 H), 9.01 (s, 1 H), 9.35 (s, 1 H).

實施例85-132：1-[6-(4-{2-[(環丙基甲基)(甲基)胺基]-1，3-噻唑-5-基}苯氧基)-3-吡啶基]-3-[3-(三氟甲基)苯基]脲 Examples 85-132: 1-[6-(4-{2-[(Cyclopropylmethyl)(methyl)amino]-1,3-thiazol-5-yl}phenoxy)-3- Pyridyl]-3-[3-(trifluoromethyl)phenyl]urea

TLC：Rf 0.49(己烷：乙酸乙酯=1：2)；1H-NMR(DMSO-d6)：δ 0.27-0.32(m，2H)，0.46-0.51(m，2H)，1.03-1.16(m，1H)，3.10(s，3H)，3.35(d，2H)，7.00-7.09(m，3H)，7.30(d，1H)，7.44-7.53(m，4H)，7.59(d，1H)，7.98(d，1H)，8.01(d，1H)，8.19(d，1H)，8.87(s，1H)，9.13(s，1H)。 TLC: Rf 0.49 (hexane: ethyl acetate = 1:2); 1 H-NMR (DMSO-d 6 ): δ 0.27-0.32 (m, 2H), 0.46-0.51 (m, 2H), 1.03-1.16 (m, 1H), 3.10 (s, 3H), 3.35 (d, 2H), 7.00-7.09 (m, 3H), 7.30 (d, 1H), 7.44 - 7.53 (m, 4H), 7.59 (d, 1H) ), 7.98 (d, 1H), 8.01 (d, 1H), 8.19 (d, 1H), 8.87 (s, 1H), 9.13 (s, 1H).

實施例85-133：1-(5-甲氧基-6-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)-3-[2-苯基-5-(三氟甲基)-3-吡啶基]脲 Example 85-133: 1-(5-Methoxy-6-{4-[2-(2-o-oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy }-3-pyridyl)-3-[2-phenyl-5-(trifluoromethyl)-3-pyridyl]urea

TLC：Rf 0.67(乙酸乙酯)； 1H-NMR(DMSO-d6)：δ 2.11-2.21(m，2 H)，2.63(t，2 H)，3.84(s，3 H)，4.04(t，2 H)，7.01-7.07(m，2 H)，7.51-7.68(m，8 H)，7.78(d，1 H)，7.84(s，1 H)，8.30(s，1 H)，8.69-8.73(m，1 H)，8.78-8.83(m，1 H)，9.46(s，1 H)。 TLC: Rf 0.67 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 2.11-2.21. (m, 2 H), 2.63 (t, 2 H), 3.84 (s, 3 H), 4.04 ( t,2 H), 7.01-7.07 (m, 2 H), 7.51-7.68 (m, 8 H), 7.78 (d, 1 H), 7.84 (s, 1 H), 8.30 (s, 1 H), 8.69-8.73 (m, 1 H), 8.78-8.83 (m, 1 H), 9.46 (s, 1 H).

實施例85-134：1-[2-(4-{2-[(四氫-2H-吡喃-4-基甲基)胺基]-1，3-噻唑-5-基}苯氧基)-5-嘧啶基]-3-[3-(三氟甲基)苯基]脲 Example 85-134: 1-[2-(4-{2-[(tetrahydro-2H-pyran-4-ylmethyl)amino]-1,3-thiazol-5-yl}phenoxy )-5-pyrimidinyl]-3-[3-(trifluoromethyl)phenyl]urea

TLC：Rf 0.49(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 1.14-1.23(m，2 H)，1.62(d，2 H)，1.75-1.95(m，1 H)，3.14(t，2 H)，3.25(dd，2 H)，3.85(dd，2 H)，7.14(d，2 H)，7.32(d，1 H)，7.41-7.55(m，4 H)，7.61(d，1 H)，7.82(t，1 H)，7.96(s，1 H)，8.69(s，2 H)，8.95(s，1 H)，9.29(s，1 H)。 TLC: Rf 0.49 (ethyl acetate); 1 H-NMR (DMSO -d 6): δ 1.14-1.23 (m, 2 H), 1.62 (d, 2 H), 1.75-1.95 (m, 1 H), 3.14(t, 2 H), 3.25 (dd, 2 H), 3.85 (dd, 2 H), 7.14 (d, 2 H), 7.32 (d, 1 H), 7.41-7.55 (m, 4 H), 7.61 (d, 1 H), 7.82 (t, 1 H), 7.96 (s, 1 H), 8.69 (s, 2 H), 8.95 (s, 1 H), 9.29 (s, 1 H).

實施例85-135：1-[2-(2-甲基-3-吡啶基)-5-(三氟甲基)苯基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 85-135: 1-[2-(2-methyl-3-pyridyl)-5-(trifluoromethyl)phenyl]-3-(2-{4-[2-(2- side) Oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.34(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 2.10-2.21(m，2 H)，2.24(s，3 H)，2.64(t，2 H)，4.15(t，2 H)，7.21(d，2 H)，7.35-7.43(m，2 H)，7.47(d，1 H)，7.62(dd，1 H)，7.66(d，2 H)，7.86(s，1 H)，7.89(s，1 H)，8.52(s，1 H)，8.59(dd，1 H)，8.64(s，2 H)，9.28(s，1 H)。 TLC: Rf 0.34 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 2.10-2.21 (m, 2 H), 2.24 (s, 3 H), 2.64 (t, 2 H), 4.15 ( t,2 H), 7.21 (d, 2 H), 7.35-7.43 (m, 2 H), 7.47 (d, 1 H), 7.62 (dd, 1 H), 7.66 (d, 2 H), 7.86 ( s, 1 H), 7.89 (s, 1 H), 8.52 (s, 1 H), 8.59 (dd, 1 H), 8.64 (s, 2 H), 9.28 (s, 1 H).

實施例85-136：1-[2-(4-甲基-3-吡啶基)-5-(三氟甲基)苯基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 85-136: 1-[2-(4-Methyl-3-pyridyl)-5-(trifluoromethyl)phenyl]-3-(2-{4-[2-(2- side) Oxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.34(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 2.07(s，3 H)，2.10-2.21(m，2 H)，2.64(t， 2 H)，4.15(t，2 H)，7.21(d，2 H)，7.38(d，1 H)，7.43(d，1 H)，7.48(dd，1 H)，7.66(d，2 H)，7.89(s，1 H)，7.90(s，1 H)，8.36(s，1 H)，8.50(s，1 H)，8.56(d，1 H)，8.63(s，2 H)，9.26(s，1 H)。 TLC: Rf 0.34 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 2.07 (s, 3 H), 2.10-2.21 (m, 2 H), 2.64 (t, 2 H), 4.15 ( t, 2 H), 7.21 (d, 2 H), 7.38 (d, 1 H), 7.43 (d, 1 H), 7.48 (dd, 1 H), 7.66 (d, 2 H), 7.89 (s, 1 H), 7.90 (s, 1 H), 8.36 (s, 1 H), 8.50 (s, 1 H), 8.56 (d, 1 H), 8.63 (s, 2 H), 9.26 (s, 1 H) ).

實施例85-137：1-(2-{4-[2-(1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[3-(三氟甲基)苯基]脲 Example 85-137: 1-(2-{4-[2-(1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-[3 -(trifluoromethyl)phenyl]urea

TLC：Rf 0.50(己烷：乙酸乙酯=1：1)；1H-NMR(DMSO-d6)：δ 1.92-2.03(m，4 H)，3.36-3.48(m，4 H)，7.15(d，2 H)，7.32(d，1 H)，7.47-7.63(m，5 H)，7.97(s，1 H)，8.70(s，2 H)，9.00(s，1 H)，9.32(s，1 H)。 TLC: Rf 0.50 (hexane: ethyl acetate = 1: 1); 1 H -NMR (DMSO-d 6): δ 1.92-2.03 (m, 4 H), 3.36-3.48 (m, 4 H), 7.15 (d, 2 H), 7.32 (d, 1 H), 7.47-7.63 (m, 5 H), 7.97 (s, 1 H), 8.70 (s, 2 H), 9.00 (s, 1 H), 9.32 (s, 1 H).

實施例85-138：1-(2-{4-[2-(1-哌啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[3-(三氟甲基)苯基]脲 Example 85-138: 1-(2-{4-[2-(1-piperidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-[3 -(trifluoromethyl)phenyl]urea

TLC：Rf 0.25(己烷：乙酸乙酯=1：1)；1H-NMR(DMSO-d6)：δ 1.52-1.67(m，6 H)，3.40-3.50(m，4 H)，7.16(d，2 H)，7.31(d，1 H)，7.47-7.62(m，5 H)，7.96(s，1 H)，8.70(s，2 H)，8.96(s，1 H)，9.29(s，1 H)。 TLC: Rf 0.25 (hexane: ethyl acetate = 1:1); 1 H-NMR (DMSO-d 6 ): δ 1.52-1.67 (m, 6 H), 3.40 - 3.50 (m, 4 H), 7.16 (d, 2 H), 7.31 (d, 1 H), 7.47-7.62 (m, 5 H), 7.96 (s, 1 H), 8.70 (s, 2 H), 8.96 (s, 1 H), 9.29 (s, 1 H).

實施例85-139：1-(2-{4-[2-(4-嗎啉基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[3-(三氟甲基)苯基]脲 Examples 85-139: 1-(2-{4-[2-(4-morpholino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-[3 -(trifluoromethyl)phenyl]urea

TLC：Rf 0.14(己烷：乙酸乙酯=1：1)；1H-NMR(DMSO-d6)：δ 3.37-3.45(m，4 H)，3.67-3.76(m，4 H)，7.18(d，2 H)，7.32(d，1 H)，7.51-7.65(m，5 H)，7.97(s，1 H)，8.71(s， 2 H)，8.97(s，1 H)，9.30(s，1 H)。 TLC: Rf 0.14 (hexane: ethyl acetate = 1:1); 1 H-NMR (DMSO-d 6 ): δ 3.37 - 3.45 (m, 4 H), 3.67-3.76 (m, 4 H), 7.18 (d, 2 H), 7.32 (d, 1 H), 7.51-7.65 (m, 5 H), 7.97 (s, 1 H), 8.71 (s, 2 H), 8.97 (s, 1 H), 9.30 (s, 1 H).

實施例85-140：1-(5-氟-2，3’-二吡啶-3-基)-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 85-140: 1-(5-Fluoro-2,3'-dipyridin-3-yl)-3-(2-{4-[2-(2-o-oxy-1-pyrrolidinyl) -1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.19(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 2.10-2.20(m，2 H)，2.65(t，2 H)，4.07(t，2 H)，7.21(d，2 H)，7.54(dd，1 H)，7.66(d，2 H)，7.86(s，1 H)，7.97-8.00(m，1 H)，8.31(dd，1 H)，8.42(d，1 H)，8.46(s，1 H)，8.66-8.67(m，3 H)，8.76(d，1 H)，9.30(s，1 H)。 TLC: Rf 0.19 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 2.10-2.20 (m, 2 H), 2.65 (t, 2 H), 4.07 (t, 2 H), 7.21. d, 2 H), 7.54 (dd, 1 H), 7.66 (d, 2 H), 7.86 (s, 1 H), 7.97-8.00 (m, 1 H), 8.31 (dd, 1 H), 8.42 ( d,1 H), 8.46 (s, 1 H), 8.66-8.67 (m, 3 H), 8.76 (d, 1 H), 9.30 (s, 1 H).

實施例85-141：1-(2-{4-[2-(1-氮雜環丁烷基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[3-(三氟甲基)苯基]脲 Example 85-141:1-(2-{4-[2-(1-Azetidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3 -[3-(trifluoromethyl)phenyl]urea

TLC：Rf 0.64(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 2.39-2.44(m，2 H)，4.03(t，4 H)，7.16(d，2 H)，7.32(d，1 H)，7.48-7.63(m，5 H)，7.97(s，1 H)，8.70(s，2 H)，8.96(s，1 H)，9.30(s，1 H)。 TLC: Rf 0.64 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 2.39-2.44 (m, 2 H), 4.03 (t, 4 H), 7.16 (d, 2 H), 7.32 ( d, 1 H), 7.48-7.63 (m, 5 H), 7.97 (s, 1 H), 8.70 (s, 2 H), 8.96 (s, 1 H), 9.30 (s, 1 H).

實施例85-142：1-[6-(4-{2-[(環丙基甲基)(甲基)胺基]-1，3-噻唑-5-基}苯氧基)-3-吡啶基]-3-[3’，4’-二甲基-4-(三氟甲基)-2-聯苯基]脲 Example 85-142: 1-[6-(4-{2-[(Cyclopropylmethyl)(methyl)amino]-1,3-thiazol-5-yl}phenoxy)-3- Pyridyl]-3-[3',4'-dimethyl-4-(trifluoromethyl)-2-biphenyl]urea

TLC：Rf 0.45(己烷：乙酸乙酯=1：1)；1H-NMR(DMSO-d6)：δ 0.27-0.32(m，2 H)，0.46-0.52(m，2 H)，1.03-1.16(m，1 H)，2.29(s，6 H)，3.10(s，3 H)，3.35(d，2 H)，6.97-7.06(m，3 H)，7.14(dd，1 H)，7.20(s，1 H)，7.29-7.50(m，6 H)，7.88(s，1 H)，7.99(dd，1 H)，8.08(d，1 H)，8.47(s，1 H)，9.35(s，1 H)。 TLC: Rf 0.45 (hexane: ethyl acetate = 1:1); 1 H-NMR (DMSO-d 6 ): δ 0.27-0.32 (m, 2 H), 0.46-0.52 (m, 2 H), 1.03 -1.16 (m, 1 H), 2.29 (s, 6 H), 3.10 (s, 3 H), 3.35 (d, 2 H), 6.97-7.06 (m, 3 H), 7.14 (dd, 1 H) , 7.20 (s, 1 H), 7.29-7.50 (m, 6 H), 7.88 (s, 1 H), 7.99 (dd, 1 H), 8.08 (d, 1 H), 8.47 (s, 1 H) , 9.35 (s, 1 H).

實施例85-143：1-[2-(5-甲基-3-吡啶基)-5-(三氟甲基)苯 基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 85-143: 1-[2-(5-Methyl-3-pyridyl)-5-(trifluoromethyl)benzene 3-(2-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.35(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 2.10-2.22(m，2 H)，2.38(s，3 H)，2.64(t，2 H)，4.05(t，2 H)，7.21(d，2 H)，7.42-7.52(m，2 H)，7.66(d，2 H)，7.70(s，1 H)，7.88(s，1 H)，8.18(s，1 H)，8.42(dd，2 H)，8.51(s，1 H)，8.64(s，2 H)，9.27(s，1 H)。 TLC: Rf 0.35 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 2.10-2.22 (m, 2 H), 2.38 (s, 3 H), 2.64 (t, 2 H), 4.05 ( t,2 H), 7.21 (d, 2 H), 7.42-7.52 (m, 2 H), 7.66 (d, 2 H), 7.70 (s, 1 H), 7.88 (s, 1 H), 8.18 ( s, 1 H), 8.42 (dd, 2 H), 8.51 (s, 1 H), 8.64 (s, 2 H), 9.27 (s, 1 H).

實施例85-144：1-[6-(4-{2-[乙基(甲基)胺基]-1，3-噻唑-5-基}苯氧基)-3-吡啶基]-3-[3-(三氟甲基)苯基]脲 Example 85-144: 1-[6-(4-{2-[Ethyl(methyl)amino]-1,3-thiazol-5-yl}phenoxy)-3-pyridyl]-3 -[3-(trifluoromethyl)phenyl]urea

TLC：Rf 0.49(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 1.15(t，3 H)，3.03(s，3 H)，3.49(q，2 H)，7.01(d，1 H)，7.06(d，2 H)，7.29(d，1 H)，7.45-7.70(m，5 H)，7.97(s，1 H)，8.01(d，1 H)，8.18(d，1 H)，8.87(s，1 H)，9.12(s，1 H)。 TLC: Rf 0.49 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 1.15 (t, 3 H), 3.03 (s, 3 H), 3.49 (q, 2 H), 7.01 (d, 1 H), 7.06 (d, 2 H), 7.29 (d, 1 H), 7.45-7.70 (m, 5 H), 7.97 (s, 1 H), 8.01 (d, 1 H), 8.18 (d, 1 H), 8.87 (s, 1 H), 9.12 (s, 1 H).

實施例85-145：1-[6-(4-{2-[(2-甲氧基乙基)胺基]-1，3-噻唑-5-基}苯氧基)-3-吡啶基]-3-[3-(三氟甲基)苯基]脲 Example 85-145: 1-[6-(4-{2-[(2-Methoxyethyl)amino]-1,3-1,3-thiazol-5-yl}phenoxy)-3-pyridyl ]-3-[3-(trifluoromethyl)phenyl]urea

TLC：Rf 0.49(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 3.27(s，3 H)，3.40-3.50(m，4 H)，6.98(d，1 H)，7.04(d，2 H)，7.26(d，1 H)，7.38(s，1 H)，7.44(d，2 H)，7.47(t，1 H)，7.65(d，1 H)，7.79(t，1 H)，7.97-8.05(m，2 H)，8.24(d，1 H)，8.42(s，1 H)，10.3(br s，1 H)。 TLC: Rf 0.49 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 3.27 (s, 3 H), 3.40 - 3.50 (m, 4 H), 6.98 (d, 1 H), 7.04 ( d, 2 H), 7.26 (d, 1 H), 7.38 (s, 1 H), 7.44 (d, 2 H), 7.47 (t, 1 H), 7.65 (d, 1 H), 7.79 (t, 1 H), 7.97-8.05 (m, 2 H), 8.24 (d, 1 H), 8.42 (s, 1 H), 10.3 (br s, 1 H).

實施例85-146：1-(2-{4-[2-(二甲胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-(1H-吡唑-1-基)-5-(三氟甲基)苯基]脲 Example 85-146: 1-(2-{4-[2-(Dimethylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-[2- (1H-pyrazol-1-yl)-5-(trifluoromethyl)phenyl]urea

TLC：Rf 0.62(二氯甲烷：乙酸乙酯：甲醇=8：4：1)； 1H-NMR(DMSO-d6)：δ 3.07(s，6 H)，6.67(t，1 H)，7.15(d，2 H)，7.45-7.55(m，4 H)，7.75(d，1 H)，7.95(d，1 H)，8.41(d，1 H)，8.58(d，1 H)，8.68(s，2 H)，9.69(s，1 H)，9.94(s，1 H)。 TLC: Rf 0.62 (dichloromethane: ethyl acetate: methanol = 8: 4: 1); 1 H-NMR (DMSO-d 6): δ 3.07 (s, 6 H), 6.67 (t, 1 H), 7.15(d,2H), 7.45-7.55 (m, 4 H), 7.75 (d, 1 H), 7.95 (d, 1 H), 8.41 (d, 1 H), 8.58 (d, 1 H), 8.68 (s, 2 H), 9.69 (s, 1 H), 9.94 (s, 1 H).

實施例85-147：1-(3，5-二氟苯基)-3-(2-{4-[2-(二甲胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 85-147: 1-(3,5-Difluorophenyl)-3-(2-{4-[2-(dimethylamino)-1,3-thiazol-5-yl]phenoxy }-5-pyrimidinyl)urea

TLC：Rf 0.35(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 3.07(s，6H)，6.81(tt，1H)，7.12-7.24(m，4H)，7.49(d，2H)，7.55(s，1H)，8.69(s，2H)，9.01(s，1H)，9.34(s，1H)。 TLC: Rf 0.35 (ethyl acetate); 1 H-NMR (DMSO -d 6): δ 3.07 (s, 6H), 6.81 (tt, 1H), 7.12-7.24 (m, 4H), 7.49 (d, 2H ), 7.55 (s, 1H), 8.69 (s, 2H), 9.01 (s, 1H), 9.34 (s, 1H).

實施例85-148：1-[2-氯-4-(三氟甲基)苯基]-3-(2-{4-[2-(二甲胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 85-148: 1-[2-Chloro-4-(trifluoromethyl)phenyl]-3-(2-{4-[2-(dimethylamino)-1,3-thiazole-5 -yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.27(己烷：乙酸乙酯=1：2)；1H-NMR(DMSO-d6)：δ 3.07(s，6 H)，7.17(d，2 H)，7.50(d，2 H)，7.55(s，1 H)，7.69(dd，1 H)，7.89(d，1 H)，8.42(d，1 H)，8.72(s，2 H)，8.79(s，1 H)，9.75(s，1 H)。 TLC: Rf 0.27 (hexane: ethyl acetate = 1:2); 1 H-NMR (DMSO-d 6 ): δ 3.07 (s, 6 H), 7.17 (d, 2 H), 7.50 (d, 2) H), 7.55 (s, 1 H), 7.69 (dd, 1 H), 7.89 (d, 1 H), 8.42 (d, 1 H), 8.72 (s, 2 H), 8.79 (s, 1 H) , 9.75 (s, 1 H).

實施例85-149：1-[5-氟-2-(4-吡啶基)苯基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 85-149: 1-[5-Fluoro-2-(4-pyridyl)phenyl]-3-(2-{4-[2-(2-o-oxy-1-pyrrolidinyl)- 1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.35(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 2.11-2.22(m，2 H)，2.64(t，2 H)，4.05(t，2 H)，7.03(tt，1 H)，7.22(d，2 H)，7.31(dd，1 H)，7.44(d，2 H)，7.66(d，2 H)，7.83-7.91(m，2 H)，8.13(s，1 H)，8.64(s，2 H)，8.66-8.72(m，2 H)，9.23(s，1 H)。 TLC: Rf 0.35 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 2.11-2.22 (m, 2 H), 2.64 (t, 2 H), 4.05 (t, 2 H), 7.03 ( Tt, 1 H), 7.22 (d, 2 H), 7.31 (dd, 1 H), 7.44 (d, 2 H), 7.66 (d, 2 H), 7.83-7.91 (m, 2 H), 8.13 ( s, 1 H), 8.64 (s, 2 H), 8.66-8.72 (m, 2 H), 9.23 (s, 1 H).

實施例85-150：1-(2-{4-[2-(3-羥基-1-氮雜環丁烷基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[3-(三氟甲基)苯基]脲 Example 85-150: 1-(2-{4-[2-(3-Hydroxy-1-azetidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidine Benzyl-3-(3-(trifluoromethyl)phenyl]urea

TLC：Rf 0.37(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 3.77-3.81(m，2 H)，4.21-4.25(m，2 H)，4.55-4.70(m，1 H)，5.83(d，1 H)，7.16(d，2 H)，7.31(d，1 H)，7.48-7.62(m，4 H)，7.96(s，1 H)，8.70(s，2 H)，8.96(s，1 H)，9.29(s，1 H)。 TLC: Rf 0.37 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 3.77-3.81 (m, 2 H), 4.21-4.25 (m, 2 H), 4.55 - 4.70 (m, 1 H) ), 5.83 (d, 1 H), 7.16 (d, 2 H), 7.31 (d, 1 H), 7.48-7.62 (m, 4 H), 7.96 (s, 1 H), 8.70 (s, 2 H) ), 8.96 (s, 1 H), 9.29 (s, 1 H).

實施例85-151：1-[2-(1-甲基-1H-咪唑-4-基)-5-(三氟甲基)-3-吡啶基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 85-151:1-[2-(1-Methyl-1H-imidazol-4-yl)-5-(trifluoromethyl)-3-pyridyl]-3-(2-{4-[ 2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.44(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 2.10-2.22(m，2 H)，2.64(t，2 H)，3.80(s，3 H)，4.05(t，2 H)，7.24(d，2 H)，7.68(d，2 H)，7.89(s，1 H)，7.97(d，2 H)，8.49(d，1 H)，8.76(s，2 H)，8.93(d，1 H)，10.1(s，1 H)，12.0(s，1 H)。 TLC: Rf 0.44 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 2.10-2.22 (m, 2 H), 2.64 (t, 2 H), 3.80 (s, 3 H), 4.05 ( t,2 H), 7.24 (d, 2 H), 7.68 (d, 2 H), 7.89 (s, 1 H), 7.97 (d, 2 H), 8.49 (d, 1 H), 8.76 (s, 2 H), 8.93 (d, 1 H), 10.1 (s, 1 H), 12.0 (s, 1 H).

實施例85-152：1-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[5-(三氟甲基)-2，2’-二吡啶-3-基]脲 Example 85-152: 1-(2-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl )-3-[5-(trifluoromethyl)-2,2'-dipyridin-3-yl]urea

TLC：Rf 0.18(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 2.10-2.20(m，2 H)，2.64(t，2 H)，4.05(t，2 H)，7.24(d，2 H)，7.61-7.69(m，3 H)，7.90(s，1 H)，8.08-8.14(m，1 H)，8.57(d，1 H)，8.70-8.80(m，4 H)，9.12-9.17(m，1 H)，10.2(s，1 H)，12.8(s，1 H)。 TLC: Rf 0.18 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 2.10-2.20 (m, 2 H), 2.64 (t, 2 H), 4.05 (t, 2 H), 7.24 ( d, 2 H), 7.61-7.69 (m, 3 H), 7.90 (s, 1 H), 8.08-8.14 (m, 1 H), 8.57 (d, 1 H), 8.70-8.80 (m, 4 H ), 9.12-9.17 (m, 1 H), 10.2 (s, 1 H), 12.8 (s, 1 H).

實施例85-153：1-(2-{4-[2-(1-氮雜環丁烷基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-(2，6-二氟苯基)脲 Example 85-153: 1-(2-{4-[2-(1-azetidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3 -(2,6-difluorophenyl)urea

TLC：Rf 0.69(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 2.36-2.58(m，2 H)，4.03(t，4 H)，7.16(m，4 H)，7.25-7.40(m，1 H)，7.48(d，2 H)，7.53(s，1 H)，8.40(s，1 H)，8.68(s，2 H)，9.16(s，1 H)。 TLC: Rf 0.69 (ethyl acetate); 1 H-NMR (DMSO -d 6): δ 2.36-2.58 (m, 2 H), 4.03 (t, 4 H), 7.16 (m, 4 H), 7.25- 7.40 (m, 1 H), 7.48 (d, 2 H), 7.53 (s, 1 H), 8.40 (s, 1 H), 8.68 (s, 2 H), 9.16 (s, 1 H).

實施例85-154：1-(2-{4-[2-(1-氮雜環丁烷基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-(2，4-二氟苯基)脲 Examples 85-154: 1-(2-{4-[2-(1-Azetidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3 -(2,4-difluorophenyl)urea

TLC：Rf 0.75(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 2.36-2.58(m，2 H)，4.03(t，4 H)，7.04(dt，1 H)，7.16(d，2 H)，7.31(dt，1 H)，7.49(d，2 H)，7.54(s，1 H)，7.92-8.02(m，1 H)，8.70(s，3 H)，9.14(s，1 H)。 TLC: Rf 0.75 (ethyl acetate); 1 H-NMR (DMSO -d 6): δ 2.36-2.58 (m, 2 H), 4.03 (t, 4 H), 7.04 (dt, 1 H), 7.16 ( d, 2 H), 7.31 (dt, 1 H), 7.49 (d, 2 H), 7.54 (s, 1 H), 7.92-8.02 (m, 1 H), 8.70 (s, 3 H), 9.14 ( s, 1 H).

實施例85-155：1-[5-氟-2-(2-吡啶基)苯基]-3-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 85-155: 1-[5-Fluoro-2-(2-pyridyl)phenyl]-3-(2-{4-[2-(2-o-oxy-1-pyrrolidinyl)- 1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.67(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 2.10-2.22(m，2 H)，2.64(t，2 H)，4.05(t，2 H)，6.85-7.02(m，1 H)，7.22(d，2 H)，7.45-7.50(m，1 H)，7.68(d，2 H)，7.80-8.05(m，4 H)，8.11(dd，1 H)，8.70(s，2 H)，8.71(d，1 H)，9.88(s，1 H)，11.7(s，1 H)。 TLC: Rf 0.67 (ethyl acetate); 1 H-NMR (DMSO -d 6): δ 2.10-2.22 (m, 2 H), 2.64 (t, 2 H), 4.05 (t, 2 H), 6.85- 7.02 (m, 1 H), 7.22 (d, 2 H), 7.45-7.50 (m, 1 H), 7.68 (d, 2 H), 7.80-8.05 (m, 4 H), 8.11 (dd, 1 H) ), 8.70 (s, 2 H), 8.71 (d, 1 H), 9.88 (s, 1 H), 11.7 (s, 1 H).

實施例85-156：1-(2-{4-[2-(1-氮雜環丁烷基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-(3，5-二氟苯基)脲 Example 85-156: 1-(2-{4-[2-(1-azetidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3 -(3,5-difluorophenyl)urea

TLC：Rf 0.73(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 2.39-2.49(m，2 H)，4.03(t，4 H)，6.81(t，1 H)，7.15-7.21(m，4 H)，7.48-7.54(m，3 H)，8.69(s，2 H)，9.02(s， 1 H)，9.35(s，1 H)。 TLC: Rf 0.73 (ethyl acetate); 1 H-NMR (DMSO -d 6): δ 2.39-2.49 (m, 2 H), 4.03 (t, 4 H), 6.81 (t, 1 H), 7.15- 7.21 (m, 4 H), 7.48-7.54 (m, 3 H), 8.69 (s, 2 H), 9.02 (s, 1 H), 9.35 (s, 1 H).

實施例85-157：1-(2-{4-[2-(1-氮雜環丁烷基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[3-氟-5-(三氟甲基)苯基]脲 Example 85-157: 1-(2-{4-[2-(1-Azetidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3 -[3-Fluoro-5-(trifluoromethyl)phenyl]urea

TLC：Rf 0.69(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 2.37-2.49(m，2 H)，4.03(t，4 H)，7.16(d，2 H)，7.25(d，1 H)，7.49-7.70(m，5 H)，8.70(s，2 H)，9.09(s，1 H)，9.50(s，1 H)。 TLC: Rf 0.69 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 2.37-2.49 (m, 2 H), 4.03 (t, 4 H), 7.16 (d, 2 H), 7.25 ( d, 1 H), 7.49-7.70 (m, 5 H), 8.70 (s, 2 H), 9.09 (s, 1 H), 9.50 (s, 1 H).

實施例85-158：1-(2-{4-[2-(1-氮雜環丁烷基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[4-甲基-3-(三氟甲基)苯基]脲 Example 85-158: 1-(2-{4-[2-(1-azetidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3 -[4-methyl-3-(trifluoromethyl)phenyl]urea

TLC：Rf 0.69(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 2.36-2.49(m，5 H)，4.03(t，4 H)，7.16(d，2 H)，7.34(d，1 H)，7.48-7.54(m，4 H)，7.88(s，1 H)，8.69(d，2 H)，8.91(s，1 H)，9.17(s，1 H)。 TLC: Rf 0.69 (ethyl acetate); 1 H-NMR (DMSO -d 6): δ 2.36-2.49 (m, 5 H), 4.03 (t, 4 H), 7.16 (d, 2 H), 7.34 ( d,1 H), 7.48-7.54 (m, 4 H), 7.88 (s, 1 H), 8.69 (d, 2 H), 8.91 (s, 1 H), 9.17 (s, 1 H).

實施例85-159：1-(2-{4-[2-(1-氮雜環丁烷基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-氯-4-(三氟甲基)苯基]脲 Example 85-159: 1-(2-{4-[2-(1-azetidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3 -[2-chloro-4-(trifluoromethyl)phenyl]urea

TLC：Rf 0.67(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 2.39-2.44(m，2 H)，4.03(t，4 H)，7.17(d，2 H)，7.47-7.54(m，3 H)，7.65-7.75(m，1 H)，7.88(s，1 H)，8.41-8.43(m，1 H)，8.73(s，2 H)，9.04(br s，1 H)，9.60(br s，1 H)。 TLC: Rf 0.67 (ethyl acetate); 1 H-NMR (DMSO -d 6): δ 2.39-2.44 (m, 2 H), 4.03 (t, 4 H), 7.17 (d, 2 H), 7.47- 7.54 (m, 3 H), 7.65-7.75 (m, 1 H), 7.88 (s, 1 H), 8.41-8.43 (m, 1 H), 8.73 (s, 2 H), 9.04 (br s, 1) H), 9.60 (br s, 1 H).

實施例85-160：1-(2-{4-[2-(1-氮雜環丁烷基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-(2，5-二氟苯基)脲 Example 85-160: 1-(2-{4-[2-(1-Azetidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3 -(2,5-difluorophenyl)urea

TLC：Rf 0.60(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 2.42(quin，2 H)，4.03(t，4 H)，6.79-6.90(m，1 H)，7.17(d，2 H)，7.29(ddd，1 H)，7.50(d，2 H)，7.54(s，1 H)，7.96(ddd，1 H)，8.71(s，2 H)，8.95(s，1 H)，9.25(s，1 H)。 TLC: Rf 0.60 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 2.42 ( s, 2 H), 4.03 (t, 4 H), 6.79 - 6.90 (m, 1 H), 7.17 ( d, 2 H), 7.29 (ddd, 1 H), 7.50 (d, 2 H), 7.54 (s, 1 H), 7.96 (ddd, 1 H), 8.71 (s, 2 H), 8.95 (s, 1 H), 9.25 (s, 1 H).

實施例85-161：1-(2-{4-[2-(1-氮雜環丁烷基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-(3，4-二氟苯基)脲 Example 85-161:1-(2-{4-[2-(1-Azetidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3 -(3,4-difluorophenyl)urea

TLC：Rf 0.50(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 2.42(quin，2 H)，4.03(t，4 H)，7.10-7.20(m，3 H)，7.31(dd，1 H)，7.49(d，2 H)，7.54(s，1 H)，7.63(ddd，1 H)，8.68(s，2 H)，8.95-9.60(br s，2 H)。 TLC: Rf 0.50 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 2.42 ( s, 2 H), 4.03 (t, 4 H), 7.10-7.20 (m, 3 H), 7.31 ( Dd, 1 H), 7.49 (d, 2 H), 7.54 (s, 1 H), 7.63 (ddd, 1 H), 8.68 (s, 2 H), 8.95-9.60 (br s, 2 H).

實施例85-162：1-(2-{4-[2-(1-氮雜環丁烷基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-(2-氟苯基)脲 Example 85-162: 1-(2-{4-[2-(1-Azetidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3 -(2-fluorophenyl)urea

TLC：Rf 0.62(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 2.42(quin，2 H)，4.03(t，4 H)，6.98-7.08(m，1 H)，7.10-7.30(m，4 H)，7.50(d，2 H)，7.54(s，1 H)，8.06(dt，1 H)，8.71(s，2 H)，8.73(s，1 H)，9.19(s，1 H)。 TLC: Rf 0.62 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 2.42 ( s, 2 H), 4.03 (t, 4 H), 6.98 - 7.08 (m, 1 H), 7.10- 7.30 (m, 4 H), 7.50 (d, 2 H), 7.54 (s, 1 H), 8.06 (dt, 1 H), 8.71 (s, 2 H), 8.73 (s, 1 H), 9.19 ( s, 1 H).

實施例85-163：1-(2-{4-[2-(3-羥基-3-甲基-1-氮雜環丁烷基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[3-(三氟甲基)苯基]脲 Examples 85-163: 1-(2-{4-[2-(3-Hydroxy-3-methyl-1-azetidinyl)-1,3-thiazol-5-yl]phenoxy }-5-pyrimidinyl)-3-[3-(trifluoromethyl)phenyl]urea

TLC：Rf 0.52(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 1.44(s，3 H)，3.87-3.93(m，4 H)，5.77(s， 1 H)，7.16(d，2 H)，7.31(d，1 H)，7.49-7.65(m，5 H)，7.97(s，1 H)，8.71(s，2 H)，9.22(s，1 H)，9.53(s，1 H)。 TLC: Rf 0.52 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 1.44 (s, 3 H), 3.87-3.93 (m, 4 H), 5.77 (s, 1 H), 7.16 ( d, 2 H), 7.31 (d, 1 H), 7.49-7.65 (m, 5 H), 7.97 (s, 1 H), 8.71 (s, 2 H), 9.22 (s, 1 H), 9.53 ( s, 1 H).

實施例85-164：1-(2-{4-[2-(3，3-二氟-1-氮雜環丁烷基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[3-(三氟甲基)苯基]脲 Examples 85-164: 1-(2-{4-[2-(3,3-Difluoro-1-azetidinyl)-1,3-thiazol-5-yl]phenoxy}- 5-pyrimidinyl)-3-[3-(trifluoromethyl)phenyl]urea

TLC：Rf 0.50(己烷：乙酸乙酯=1：2)；1H-NMR(DMSO-d6)：δ 4.52(t，4 H)，7.18(d，2 H)，7.30(d，1 H)，7.47-7.64(m，5 H)，7.94-7.97(m，1 H)，8.70(s，2 H)，8.99(s，1 H)，9.31(s，1 H)。 TLC: Rf 0.50 (hexane: ethyl acetate = 1: 2); 1 H -NMR (DMSO-d 6): δ 4.52 (t, 4 H), 7.18 (d, 2 H), 7.30 (d, 1 H), 7.47-7.64 (m, 5 H), 7.94-7.97 (m, 1 H), 8.70 (s, 2 H), 8.99 (s, 1 H), 9.31 (s, 1 H).

實施例85-165：1-(2-{4-[2-(1-氮雜環丁烷基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-(4-氟苯基)脲 Examples 85-165: 1-(2-{4-[2-(1-Azetidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3 -(4-fluorophenyl)urea

TLC：Rf 0.63(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 2.38-2.54(m，2 H)，4.03(t，4 H)，7.06-7.19(m，4 H)，7.41-7.58(m，4 H)，8.65(s，1 H)，8.69(s，2 H)，8.86(s，1 H)，8.94(s，1 H)。 TLC: Rf 0.63 (ethyl acetate); 1 H-NMR (DMSO -d 6): δ 2.38-2.54 (m, 2 H), 4.03 (t, 4 H), 7.06-7.19 (m, 4 H), 7.41-7.58 (m, 4 H), 8.65 (s, 1 H), 8.69 (s, 2 H), 8.86 (s, 1 H), 8.94 (s, 1 H).

實施例85-166：1-(2-{4-[2-(1-氮雜環丁烷基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-苯基-5-(三氟甲基)-3-吡啶基]脲 Example 85-166: 1-(2-{4-[2-(1-azetidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3 -[2-phenyl-5-(trifluoromethyl)-3-pyridyl]urea

TLC：Rf 0.45(己烷：乙酸乙酯=1：4)；1H-NMR(DMSO-d6)：δ 2.40-2.49(m，2 H)，4.03(t，4 H)，7.14(d，2 H)，7.47-7.66(m，8 H)，8.41(s，1 H)，8.65(s，2 H)，8.72(s，1 H)，8.75(s，1 H)，9.44(s，1 H)。 TLC: Rf 0.45 (hexane: ethyl acetate = 1 : 4); 1 H-NMR (DMSO-d 6 ): δ 2.40 - 2.49 (m, 2 H), 4.03 (t, 4 H), 7.14 (d) , 2 H), 7.47-7.66 (m, 8 H), 8.41 (s, 1 H), 8.65 (s, 2 H), 8.72 (s, 1 H), 8.75 (s, 1 H), 9.44 (s) , 1 H).

實施例85-167：1-(2-{4-[2-(1-氮雜環丁烷基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[1-(2-甲基苯基)-3-(2-甲基-2-丙基)-1H-吡唑-5-基]脲 Examples 85-167: 1-(2-{4-[2-(1-Azetidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3 -[1-(2-methylphenyl)-3-(2-methyl-2-propyl)-1H-pyrazol-5-yl]urea

TLC：Rf 0.44(己烷：乙酸乙酯=1：4)；1H-NMR(DMSO-d6)：δ 1.26(t，9 H)，1.99(s，3 H)，2.40-2.49(m，2 H)，4.03(t，4 H)，6.33(s，1 H)，7.13(d，2 H)，7.28-7.53(m，7 H)，8.37(s，1 H)，8.61(s，2 H)，9.04(s，1 H)。 TLC: Rf 0.44 (hexane: ethyl acetate = 1 : 4); 1 H-NMR (DMSO-d 6 ): δ 1.26 (t, 9 H), 1.99 (s, 3 H), 2.40-2.49 (m) , 2 H), 4.03 (t, 4 H), 6.33 (s, 1 H), 7.13 (d, 2 H), 7.28-7.53 (m, 7 H), 8.37 (s, 1 H), 8.61 (s) , 2 H), 9.04 (s, 1 H).

實施例85-168：1-(2-{4-[2-(1-氮雜環丁烷基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-(3-吡啶基)-5-(三氟甲基)苯基]脲 Example 85-168: 1-(2-{4-[2-(1-azetidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3 -[2-(3-pyridyl)-5-(trifluoromethyl)phenyl]urea

TLC：Rf 0.58(乙酸乙酯：甲醇：19：1)；1H-NMR(DMSO-d6)：δ 2.40-2.49(m，2 H)，4.03(t，4 H)，7.14(d，2 H)，7.47-7.57(m，6 H)，7.87-7.89(m，1 H)，8.22(s，1 H)，8.37(s，1 H)，8.62-8.67(m，4 H)，9.22(s，1 H)。 TLC: Rf 0.58 (ethyl acetate: methanol: 19: 1); 1 H -NMR (DMSO-d 6): δ 2.40-2.49 (m, 2 H), 4.03 (t, 4 H), 7.14 (d, 2 H), 7.47-7.57 (m, 6 H), 7.87-7.89 (m, 1 H), 8.22 (s, 1 H), 8.37 (s, 1 H), 8.62-8.67 (m, 4 H), 9.22 (s, 1 H).

實施例85-169：1-(2-{4-[2-(1-氮雜環丁烷基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[3-(二氟甲基)苯基]脲 Examples 85-169: 1-(2-{4-[2-(1-Azetidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3 -[3-(difluoromethyl)phenyl]urea

TLC：Rf 0.44(己烷：乙酸乙酯=1：4)；1H-NMR(DMSO-d6)：δ 2.40-2.49(m，2 H)，4.03(t，4 H)，6.99(s，1 H)，7.14-7.18(m，3 H)，7.38-7.54(m，5 H)，7.76(s，1 H)，8.70(s，2 H)，8.89(s，1 H)，9.15(s，1 H)。 TLC: Rf 0.44 (hexane: ethyl acetate = 1 : 4); 1 H-NMR (DMSO-d 6 ): δ 2.40 - 2.49 (m, 2 H), 4.03 (t, 4 H), 6.99 (s) , 1 H), 7.14-7.18 (m, 3 H), 7.38-7.54 (m, 5 H), 7.76 (s, 1 H), 8.70 (s, 2 H), 8.89 (s, 1 H), 9.15 (s, 1 H).

實施例85-170：1-(2-{4-[2-(1-氮雜環丁烷基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-(2，3，5-三氟苯基)脲 Examples 85-170: 1-(2-{4-[2-(1-Azetidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3 -(2,3,5-trifluorophenyl)urea

TLC：Rf 0.59(己烷：乙酸乙酯=1：4)；1H-NMR(DMSO-d6)：δ 2.40-2.49(m，2 H)，4.13(t，4 H)，7.15-7.22 (m，3 H)，7.54(d，2 H)，7.69(s，1 H)，7.78-7.85(m，1 H)，8.71(s，2 H)，9.22(s，1 H)，9.41(s，1 H)。 TLC: Rf 0.59 (hexane: ethyl acetate = 1 : 4); 1 H-NMR (DMSO-d 6 ): δ 2.40-2.49 (m, 2 H), 4.13 (t, 4 H), 7.15-7.22 (m,3 H), 7.54 (d, 2 H), 7.69 (s, 1 H), 7.78-7.85 (m, 1 H), 8.71 (s, 2 H), 9.22 (s, 1 H), 9.41 (s, 1 H).

實施例85-171：1-(2-{4-[2-(1-氮雜環丁烷基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-氯-5-(三氟甲基)苯基]脲 Example 85-171:1-(2-{4-[2-(1-Azetidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3 -[2-chloro-5-(trifluoromethyl)phenyl]urea

TLC：Rf 0.49(己烷：乙酸乙酯=1：4)；1H-NMR(DMSO-d6)：δ 2.40-2.49(m，2 H)，4.03(t，4 H)，7.16(d，2 H)，7.37-7.40(m，1 H)，7.48-7.54(m，3 H)，7.72(d，1 H)，8.55(s，1 H)，8.72(s，2 H)，8.80(s，1 H)，9.70(s，1 H)。 TLC: Rf 0.49 (hexane: ethyl acetate = 1 : 4); 1 H-NMR (DMSO-d 6 ): δ 2.40-2.49 (m, 2 H), 4.03 (t, 4 H), 7.16 (d) , 2 H), 7.37-7.40 (m, 1 H), 7.48-7.54 (m, 3 H), 7.72 (d, 1 H), 8.55 (s, 1 H), 8.72 (s, 2 H), 8.80 (s, 1 H), 9.70 (s, 1 H).

實施例85-172：1-(2-{4-[2-(1-氮雜環丁烷基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-(2，4，6-三氟苯基)脲 Example 85-172: 1-(2-{4-[2-(1-Azetidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3 -(2,4,6-trifluorophenyl)urea

TLC：Rf 0.49(己烷：乙酸乙酯=1：4)；1H-NMR(DMSO-d6)：δ 2.35-2.49(m，2 H)，4.03(t，4 H)，7.14(d，2 H)，7.26(t，2 H)，7.48(d，2 H)，7.53(s，1 H)，8.40(s，1 H)，8.67(s，2 H)，9.20(s，1 H)。 TLC: Rf 0.49 (hexane: ethyl acetate = 1 : 4); 1 H-NMR (DMSO-d 6 ): δ 2.35-2.49 (m, 2 H), 4.03 (t, 4 H), 7.14 (d) , 2 H), 7.26 (t, 2 H), 7.48 (d, 2 H), 7.53 (s, 1 H), 8.40 (s, 1 H), 8.67 (s, 2 H), 9.20 (s, 1) H).

實施例85-173：1-(2-{4-[2-(1-氮雜環丁烷基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-氟-5-(三氟甲基)苯基]脲 Example 85-173: 1-(2-{4-[2-(1-azetidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3 -[2-Fluoro-5-(trifluoromethyl)phenyl]urea

TLC：Rf 0.50(己烷：乙酸乙酯=1：4)；1H-NMR(DMSO-d6)：δ 2.35-2.49(m，2 H)，4.03(t，4 H)，7.16(d，2 H)，7.38-7.54(m，5 H)，8.52(d，1 H)，8.72(s，2 H)，9.19(s，2 H)。 TLC: Rf 0.50 (hexane: ethyl acetate = 1 : 4); 1 H-NMR (DMSO-d 6 ): δ 2.35-2.49 (m, 2 H), 4.03 (t, 4 H), 7.16 (d) , 2 H), 7.38-7.54 (m, 5 H), 8.52 (d, 1 H), 8.72 (s, 2 H), 9.19 (s, 2 H).

實施例85-174：1-(2-{4-[2-(1-氮雜環丁烷基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-(2，3-二氟苯基)脲 Example 85-174: 1-(2-{4-[2-(1-Azetidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3 -(2,3-difluorophenyl)urea

TLC：Rf 0.57(己烷：乙酸乙酯=1：2)；1H-NMR(DMSO-d6)：δ 2.38-2.50(m，2 H)，4.03(t，4 H)，7.02-7.21 (m，4 H)，7.49(d，2 H)，7.54(s，1 H)，7.86(t，1 H)，8.71(s，2 H)，8.94(s，1 H)，9.23(s，1 H)。 TLC: Rf 0.57 (hexane: ethyl acetate = 1: 2); 1 H -NMR (DMSO-d 6): δ 2.38-2.50 (m, 2 H), 4.03 (t, 4 H), 7.02-7.21 (m, 4 H), 7.49 (d, 2 H), 7.54 (s, 1 H), 7.86 (t, 1 H), 8.71 (s, 2 H), 8.94 (s, 1 H), 9.23 (s) , 1 H).

實施例85-175：1-(2-{4-[2-(1-氮雜環丁烷基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-(2，4，5-三氟苯基)脲 Example 85-175: 1-(2-{4-[2-(1-Azetidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3 -(2,4,5-trifluorophenyl)urea

TLC：Rf 0.36(己烷：乙酸乙酯=1：2)；1H-NMR(DMSO-d6)：δ 2.37-2.50(m，2 H)，4.03(t，4 H)，7.16(d，2 H)，7.51(d，2 H)，7.54(s，1 H)，7.59-7.70(m，1 H)，8.00-8.17(m，1 H)，8.70(s，2 H)，8.91(s，1 H)，9.20(s，1 H)。 TLC: Rf 0.36 (hexane: ethyl acetate = 1: 2); 1 H -NMR (DMSO-d 6): δ 2.37-2.50 (m, 2 H), 4.03 (t, 4 H), 7.16 (d , 2 H), 7.51 (d, 2 H), 7.54 (s, 1 H), 7.59-7.70 (m, 1 H), 8.00-8.17 (m, 1 H), 8.70 (s, 2 H), 8.91 (s, 1 H), 9.20 (s, 1 H).

實施例85-176：1-(2-{4-[2-(1-氮雜環丁烷基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[5-苯基-2-(三氟甲基)-4-吡啶基]脲 Example 85-176: 1-(2-{4-[2-(1-Azetidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3 -[5-phenyl-2-(trifluoromethyl)-4-pyridyl]urea

TLC：Rf 0.65(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 2.40-2.49(m，2 H)，4.03(t，4 H)，7.15(d，2 H)，7.50-7.60(m，8 H)，8.42(s，2 H)，8.65(s，2 H)，8.74(s，1 H)，9.71(s，1 H)。 TLC: Rf 0.65 (ethyl acetate); 1 H-NMR (DMSO -d 6): δ 2.40-2.49 (m, 2 H), 4.03 (t, 4 H), 7.15 (d, 2 H), 7.50- 7.60 (m, 8 H), 8.42 (s, 2 H), 8.65 (s, 2 H), 8.74 (s, 1 H), 9.71 (s, 1 H).

實施例85-177：1-(2-{4-[2-(1-氮雜環丁烷基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-(2，3，4-三氟苯基)脲 Example 85-177: 1-(2-{4-[2-(1-Azetidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3 -(2,3,4-trifluorophenyl)urea

TLC：Rf 0.40(己烷：乙酸乙酯=1：2)；1H-NMR(DMSO-d6)：δ 2.37-2.50(m，2 H)，4.03(t 4 H)，7.15(dd，2 H)，7.22-7.34(m，1 H)，7.50(d，2 H)，7.54(s，1 H)，7.73-7.90(m，1 H)，8.70(s，2 H)，8.89(s，1 H)，9.18(s，1 H)。 TLC: Rf 0.40 (hexane: ethyl acetate = 1: 2); 1 H -NMR (DMSO-d 6): δ 2.37-2.50 (m, 2 H), 4.03 (t 4 H), 7.15 (dd, 2 H), 7.22 - 7.34 (m, 1 H), 7.50 (d, 2 H), 7.54 (s, 1 H), 7.73-7.90 (m, 1 H), 8.70 (s, 2 H), 8.89 ( s, 1 H), 9.18 (s, 1 H).

實施例85-178：1-(2-{4-[2-(1-氮雜環丁烷基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-(2，3，5，6-四氟苯基)脲 Example 85-178: 1-(2-{4-[2-(1-Azetidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3 -(2,3,5,6-tetrafluorophenyl)urea

TLC：Rf 0.40(己烷：乙酸乙酯=1：2)；1H-NMR(DMSO-d6)：δ 2.37-2.50(m，2 H)，4.03(t，4 H)，7.15(d， 2 H)，7.50(d，2 H)，7.54(s，1 H)，7.70-7.90(m，1 H)，8.69(s，2 H)，8.87(s，1 H)，9.30(s，1 H)。 TLC: Rf 0.40 (hexane: ethyl acetate = 1: 2); 1 H -NMR (DMSO-d 6): δ 2.37-2.50 (m, 2 H), 4.03 (t, 4 H), 7.15 (d , 2 H), 7.50 (d, 2 H), 7.54 (s, 1 H), 7.70-7.90 (m, 1 H), 8.69 (s, 2 H), 8.87 (s, 1 H), 9.30 (s) , 1 H).

實施例85-179：1-(2-{4-[2-(1-氮雜環丁烷基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-(1H-1，2，3-三唑-1-基)-5-(三氟甲基)苯基]脲 Example 85-179: 1-(2-{4-[2-(1-azetidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3 -[2-(1H-1,2,3-triazol-1-yl)-5-(trifluoromethyl)phenyl]urea

TLC：Rf 0.52(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 2.37-2.51(m，2 H)，4.03(t，4 H)，7.15(dd，2 H)，7.50(d，2 H)，7.54(s，1 H)，7.61(d，1 H)，7.74(d，1 H)，8.10(d，1 H)，8.57(s，1 H)，8.65(s，2 H)，8.68-8.73(m，2 H)，9.64(s，1 H)。 TLC: Rf 0.52 (ethyl acetate); 1 H-NMR (DMSO -d 6): δ 2.37-2.51 (m, 2 H), 4.03 (t, 4 H), 7.15 (dd, 2 H), 7.50 ( d, 2 H), 7.54 (s, 1 H), 7.61 (d, 1 H), 7.74 (d, 1 H), 8.10 (d, 1 H), 8.57 (s, 1 H), 8.65 (s, 2 H), 8.68-8.73 (m, 2 H), 9.64 (s, 1 H).

實施例85-180：1-(2-{4-[2-(1-氮雜環丁烷基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-(1H-吡唑-1-基)-5-(三氟甲基)苯基]脲 Example 85-180: 1-(2-{4-[2-(1-azetidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3 -[2-(1H-pyrazol-1-yl)-5-(trifluoromethyl)phenyl]urea

TLC：Rf 0.61(二氯甲烷：乙酸乙酯：甲醇=8：4：1)；1H-NMR(DMSO-d6)：δ 2.42(quin，2 H)，4.03(t，4 H)，6.67(t，1 H)，7.16(d，2 H)，7.48-7.56(m，4 H)，7.75(d，1 H)，7.95(d，1 H)，8.41(d，1 H)，8.58(d，1 H)，8.68(s，2 H)，9.70(s，1 H)，9.95(s，1 H)。 TLC: Rf 0.61 (dichloromethane: ethyl acetate: methanol = 8: 4: 1); 1 H-NMR (DMSO-d 6): δ 2.42 (quin, 2 H), 4.03 (t, 4 H), 6.67 (t, 1 H), 7.16 (d, 2 H), 7.48-7.56 (m, 4 H), 7.75 (d, 1 H), 7.95 (d, 1 H), 8.41 (d, 1 H), 8.58 (d, 1 H), 8.68 (s, 2 H), 9.70 (s, 1 H), 9.95 (s, 1 H).

實施例85-181：1-(2-{4-[2-(1-氮雜環丁烷基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-甲基-5-(三氟甲基)苯基]脲 Example 85-181:1-(2-{4-[2-(1-azetidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3 -[2-methyl-5-(trifluoromethyl)phenyl]urea

TLC：Rf 0.28(己烷：乙酸乙酯=1：4)；1H-NMR(DMSO-d6)：δ 2.32-2.49(m，5 H)，4.03(t，4 H)，7.16(d，2 H)，7.29(d，1 H)，7.41(d，1 H)，7.49-7.54(m，3 H)，8.27(s，1 H)，8.37(s，1 H)，8.72(s，2 H)，9.32(s，1 H)。 TLC: Rf 0.28 (hexane: ethyl acetate = 1 : 4); 1 H-NMR (DMSO-d 6 ): δ 2.32-2.49 (m, 5 H), 4.03 (t, 4 H), 7.16 (d) , 2 H), 7.29 (d, 1 H), 7.41 (d, 1 H), 7.49-7.54 (m, 3 H), 8.27 (s, 1 H), 8.37 (s, 1 H), 8.72 (s , 2 H), 9.32 (s, 1 H).

實施例85-182：1-(2-{4-[2-(1-氮雜環丁烷基)-1，3-噻唑-5- 基]苯氧基}-5-嘧啶基)-3-[2-(三氟甲基)-4-吡啶基]脲 Example 85-182: 1-(2-{4-[2-(1-azetidinyl)-1,3-thiazole-5- Phenyloxy}-5-pyrimidinyl-3-[2-(trifluoromethyl)-4-pyridyl]urea

TLC：Rf 0.60(己烷：乙酸乙酯=1：4)；1H-NMR(DMSO-d6)：δ 2.37-2.49(m，2 H)，4.06(t，4 H)，7.16(d，2 H)，7.48-7.63(m，4 H)，8.02(s，1 H)，8.52(d，1 H)，8.71(s，2 H)，9.23(s，1 H)，9.82(s，1 H)。 TLC: Rf 0.60 (hexane: ethyl acetate = 1 : 4); 1 H-NMR (DMSO-d 6 ): δ 2.37-2.49 (m, 2 H), 4.06 (t, 4 H), 7.16 (d) , 2 H), 7.48-7.63 (m, 4 H), 8.02 (s, 1 H), 8.52 (d, 1 H), 8.71 (s, 2 H), 9.23 (s, 1 H), 9.82 (s , 1 H).

實施例85-183：1-(2-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-(1H-吡唑-1-基)-5-(三氟甲基)苯基]脲 Example 85-183: 1-(2-{4-[2-(propylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-[2-(1H -pyrazol-1-yl)-5-(trifluoromethyl)phenyl]urea

純度(UPLC-MS/ELSD)：99%(保持時間：0.91分鐘)；MASS(ESI，Pos.)：581(M+H)+；1H-NMR(DMSO-d6)：δ 0.91(t，3 H)，1.51-1.63(m，2 H)，3.16-3.22(m，2 H)，6.66-6.68(m，1 H)，7.11-7.15(m，2 H)，7.41-7.45(m，3 H)，7.51(dd，1 H)，7.73-7.78(m，2 H)，7.95(d，1 H)，8.44(d，1 H)，8.58(dd，1 H)，8.67(s，2 H)，9.69(s，1 H)，9.94(s，1 H)。 Purity (UPLC-MS/ELSD): 99% (holding time: 0.91 minutes); MASS (ESI, Pos.): 581 (M+H) + ; 1 H-NMR (DMSO-d 6 ): δ 0.91 (t , 3 H), 1.51-1.63 (m, 2 H), 3.16-3.22 (m, 2 H), 6.66-6.68 (m, 1 H), 7.11-7.15 (m, 2 H), 7.41-7.45 (m , 3 H), 7.51 (dd, 1 H), 7.73-7.78 (m, 2 H), 7.95 (d, 1 H), 8.44 (d, 1 H), 8.58 (dd, 1 H), 8.67 (s) , 2 H), 9.69 (s, 1 H), 9.94 (s, 1 H).

實施例85-184：1-(2-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-{5-(三氟甲基)-2-[3-(三氟甲基)-1H-吡唑-1-基]苯基}脲 Example 85-184: 1-(2-{4-[2-(propylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-{5-(three Fluoromethyl)-2-[3-(trifluoromethyl)-1H-pyrazol-1-yl]phenyl}urea

純度(UPLC-MS/ELSD)：97%(保持時間：0.97分鐘)；MASS(ESI，Pos.)：649(M+H)+；1H-NMR(DMSO-d6)：δ 0.91(t，3 H)，1.51-1.63(m，2 H)，3.16-3.22(m，2 H)，7.10-7.15(m，3 H)，7.41-7.46(m，3 H)，7.57(dd，1 H)，7.70(d，1 H)，7.76(t，1 H)，8.46-8.47(m，2 H)，8.57(s，1 H)，8.63(s，2 H)，9.45(s，1 H)。 Purity (UPLC-MS/ELSD): 97% (holding time: 0.97 minutes); MASS (ESI, Pos.): 649 (M+H) + ; 1 H-NMR (DMSO-d 6 ): δ 0.91 (t , 3 H), 1.51-1.63 (m, 2 H), 3.16-3.22 (m, 2 H), 7.10-7.15 (m, 3 H), 7.41-7.46 (m, 3 H), 7.57 (dd, 1 H), 7.70 (d, 1 H), 7.76 (t, 1 H), 8.46-8.47 (m, 2 H), 8.57 (s, 1 H), 8.63 (s, 2 H), 9.45 (s, 1) H).

實施例85-185：1-[2-(1-甲基-1H-吡唑-5-基)-5-(三氟甲基)苯基]-3-(2-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 85-185: 1-[2-(1-Methyl-1H-pyrazol-5-yl)-5-(trifluoromethyl)phenyl]-3-(2-{4-[2- (propylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

純度(UPLC-MS/ELSD)：99%(保持時間：0.89分鐘)；MASS(ESI，Pos.)：595(M+H)+；1H-NMR(DMSO-d6)：δ 0.91(t，3 H)，1.51-1.63(m，2 H)，3.16-3.22(m，2 H)，3.65(s，3 H)，6.45(d，1 H)，7.10-7.15(m，2 H)，7.42-7.51(m，5 H)，7.62(d，1 H)，7.76(t，1 H)，8.08(s，1 H)，8.55(s，1 H)，8.65(s，2 H)，9.45(s，1 H)。 Purity (UPLC-MS/ELSD): 99% (holding time: 0.89 minutes); MASS (ESI, Pos.): 595 (M+H) + ; 1 H-NMR (DMSO-d 6 ): δ 0.91 (t , 3 H), 1.51-1.63 (m, 2 H), 3.16-3.22 (m, 2 H), 3.65 (s, 3 H), 6.45 (d, 1 H), 7.10-7.15 (m, 2 H) , 7.42 - 7.51 (m, 5 H), 7.62 (d, 1 H), 7.76 (t, 1 H), 8.08 (s, 1 H), 8.55 (s, 1 H), 8.65 (s, 2 H) , 9.45 (s, 1 H).

實施例85-186：1-[2-(3-甲基-1H-吡唑-1-基)-5-(三氟甲基)苯基]-3-(2-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 85-186: 1-[2-(3-Methyl-1H-pyrazol-1-yl)-5-(trifluoromethyl)phenyl]-3-(2-{4-[2- (propylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

純度(UPLC-MS/ELSD)：96%(保持時間：0.94分鐘)；MASS(ESI，Pos.)：595(M+H)+；1H-NMR(DMSO-d6)：δ 0.91(t，3 H)，1.51-1.63(m，2 H)，2.36(s，3 H)，3.16-3.22(m，2 H)，6.45(d，1 H)，7.11-7.16(m，2 H)，7.42-7.50(m，4 H)，7.69(d，1 H)，7.76(t，1 H)，8.28(d，1 H)，8.56(d，1 H)，8.67(s，2 H)，9.80(s，1 H)，9.91(s，1 H)。 Purity (UPLC-MS/ELSD): 96% (holding time: 0.94 minutes); MASS (ESI, Pos.): 595 (M+H) + ; 1 H-NMR (DMSO-d 6 ): δ 0.91 (t , 3 H), 1.51-1.63 (m, 2 H), 2.36 (s, 3 H), 3.16-3.22 (m, 2 H), 6.45 (d, 1 H), 7.11-7.16 (m, 2 H) , 7.42-7.50 (m, 4 H), 7.69 (d, 1 H), 7.76 (t, 1 H), 8.28 (d, 1 H), 8.56 (d, 1 H), 8.67 (s, 2 H) , 9.80 (s, 1 H), 9.91 (s, 1 H).

實施例85-187：1-[2-(4-甲基-1H-吡唑-1-基)-5-(三氟甲基)苯基]-3-(2-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 85-187: 1-[2-(4-Methyl-1H-pyrazol-1-yl)-5-(trifluoromethyl)phenyl]-3-(2-{4-[2- (propylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

純度(UPLC-MS/ELSD)：100%(保持時間：0.96分鐘)；MASS(ESI，Pos.)：595(M+H)+；1H-NMR(DMSO-d6)：δ 0.91(t，3 H)，1.51-1.63(m，2 H)，2.14(s，3 H)，3.16-3.22(m，2 H)，7.11-7.16(m，2 H)，7.42-7.51(m，4 H)，7.70(d，1 H)，7.74-7.78(m，2 H)，8.18(s，1 H)，8.57(d，1 H)，8.68(s，2 H)，9.82(s，1 H)，9.95(s，1 H)。 Purity (UPLC-MS/ELSD): 100% (holding time: 0.96 minutes); MASS (ESI, Pos.): 595 (M+H) + ; 1 H-NMR (DMSO-d 6 ): δ 0.91 (t , 3 H), 1.51-1.63 (m, 2 H), 2.14 (s, 3 H), 3.16-3.22 (m, 2 H), 7.11-7.16 (m, 2 H), 7.42-7.51 (m, 4) H), 7.70 (d, 1 H), 7.74-7.78 (m, 2 H), 8.18 (s, 1 H), 8.57 (d, 1 H), 8.68 (s, 2 H), 9.82 (s, 1) H), 9.95 (s, 1 H).

實施例85-188：1-[2-(4-甲基-1H-1，2，3-三唑-1-基)-5-(三氟甲基)苯基]-3-(2-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶 基)脲 Example 85-188: 1-[2-(4-Methyl-1H-1,2,3-triazol-1-yl)-5-(trifluoromethyl)phenyl]-3-(2- {4-[2-(propylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidine Urea

純度(UPLC-MS/ELSD)：99%(保持時間：0.86分鐘)；MASS(ESI，Pos.)：596(M+H)+；1H-NMR(DMSO-d6)：δ 0.91(t，3 H)，1.51-1.63(m，2 H)，2.38(d，3 H)，3.16-3.22(m，2 H)，7.11-7.16(m，2 H)，7.42-7.46(m，3 H)，7.59(dd，1 H)，7.69(d，1 H)，7.76(t，1 H)，8.39(d，1 H)，8.64(d，1 H)，8.66(s，2 H)，8.75(s，1 H)，9.68(s，1 H)。 Purity (UPLC-MS/ELSD): 99% (holding time: 0.86 minutes); MASS (ESI, Pos.): 596 (M+H) + ; 1 H-NMR (DMSO-d 6 ): δ 0.91 (t , 3 H), 1.51-1.63 (m, 2 H), 2.38 (d, 3 H), 3.16-3.22 (m, 2 H), 7.11-7.16 (m, 2 H), 7.42-7.46 (m, 3) H), 7.59 (dd, 1 H), 7.69 (d, 1 H), 7.76 (t, 1 H), 8.39 (d, 1 H), 8.64 (d, 1 H), 8.66 (s, 2 H) , 8.75 (s, 1 H), 9.68 (s, 1 H).

實施例85-189：1-(2-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-(1H-吡唑-1-基)-4-(三氟甲基)苯基]脲 Example 85-189: 1-(2-{4-[2-(propylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-[2-(1H -pyrazol-1-yl)-4-(trifluoromethyl)phenyl]urea

純度(UPLC-MS/ELSD)：100%(保持時間：0.93分鐘)；MASS(ESI，Pos.)：581(M+H)+；1H-NMR(DMSO-d6)：δ 0.91(t，3 H)，1.51-1.63(m，2 H)，3.16-3.22(m，2 H)，6.65(t，1 H)，7.12-7.16(m，2 H)，7.41-7.46(m，3 H)，7.72-7.78(m，2 H)，7.82(d，1 H)，7.93(d，1 H)，8.40-8.43(m，2 H)，8.67(s，2 H)，9.55(s，1 H)，9.95(s，1 H)。 Purity (UPLC-MS/ELSD): 100% (holding time: 0.93 minutes); MASS (ESI, Pos.): 581 (M+H) + ; 1 H-NMR (DMSO-d 6 ): δ 0.91 (t , 3 H), 1.51-1.63 (m, 2 H), 3.16-3.22 (m, 2 H), 6.65 (t, 1 H), 7.12-7.16 (m, 2 H), 7.41-7.46 (m, 3) H), 7.72-7.78 (m, 2 H), 7.82 (d, 1 H), 7.93 (d, 1 H), 8.40-8.43 (m, 2 H), 8.67 (s, 2 H), 9.55 (s) , 1 H), 9.95 (s, 1 H).

實施例85-190：1-(2-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-(3-吡啶基)-4-(三氟甲基)苯基]脲 Example 85-190: 1-(2-{4-[2-(propylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-[2-(3 -pyridyl)-4-(trifluoromethyl)phenyl]urea

純度(UPLC-MS/ELSD)：92%(保持時間：0.81分鐘)；MASS(ESI，Pos.)：592(M+H)+；1H-NMR(DMSO-d6)：δ 0.91(t，3 H)，1.51-1.63(m，2 H)，3.16-3.22 (m，2 H)，7.11-7.15(m，2 H)，7.41-7.45(m，3 H)，7.53-7.57(m，2 H)，7.74-7.78(m，2 H)，7.88-7.92(m，1 H)，8.23(s，1 H)，8.27(d，1 H)，8.63-8.69(m，4 H)，9.27(s，1 H)。 Purity (UPLC-MS/ELSD): 92% (holding time: 0.81 minutes); MASS (ESI, Pos.): 592 (M+H) + ; 1 H-NMR (DMSO-d 6 ): δ 0.91 (t , 3 H), 1.51-1.63 (m, 2 H), 3.16-3.22 (m, 2 H), 7.11-7.15 (m, 2 H), 7.41-7.45 (m, 3 H), 7.53-7.57 (m , 2 H), 7.74-7.78 (m, 2 H), 7.88-7.92 (m, 1 H), 8.23 (s, 1 H), 8.27 (d, 1 H), 8.63-8.69 (m, 4 H) , 9.27 (s, 1 H).

實施例85-191：1-[5-氯-2-(1H-吡唑-1-基)苯基]-3-(2-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 85-191:1-[5-Chloro-2-(1H-pyrazol-1-yl)phenyl]-3-(2-{4-[2-(propylamino)-1,3-thiazole -5-yl]phenoxy}-5-pyrimidinyl)urea

純度(UPLC-MS/ELSD)：99%(保持時間：0.88分鐘)；MASS(ESI，Pos.)：547(M+H)+；1H-NMR(DMSO-d6)：δ 0.91(t，3 H)，1.51-1.63(m，2 H)，3.16-3.22(m，2 H)，6.61-6.63(m，1 H)，7.11-7.16(m，2 H)，7.22(dd，1 H)，7.42-7.46(m，3 H)，7.51(d，1 H)，7.76(t，1 H)，7.89-7.90(m，1 H)，8.25-8.28(m，2 H)，8.66(s，2 H)，9.37(s，1 H)，9.88(s，1 H)。 Purity (UPLC-MS/ELSD): 99% (holding time: 0.88 minutes); MASS (ESI, Pos.): 547 (M+H) + ; 1 H-NMR (DMSO-d 6 ): δ 0.91 (t , 3 H), 1.51-1.63 (m, 2 H), 3.16-3.22 (m, 2 H), 6.61-6.63 (m, 1 H), 7.11-7.16 (m, 2 H), 7.22 (dd, 1 H), 7.42-7.46 (m, 3 H), 7.51 (d, 1 H), 7.76 (t, 1 H), 7.89-7.90 (m, 1 H), 8.25-8.28 (m, 2 H), 8.66 (s, 2 H), 9.37 (s, 1 H), 9.88 (s, 1 H).

實施例85-192：1-[5-氯-2-(3-吡啶基)苯基]-3-(2-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 85-192: 1-[5-Chloro-2-(3-pyridyl)phenyl]-3-(2-{4-[2-(propylamino)-1,3-thiazol-5-yl Phenoxy}-5-pyrimidinyl)urea

純度(UPLC-MS/ELSD)：76%(保持時間：0.74分鐘)；MASS(ESI，Pos.)：558(M+H)+；1H-NMR(DMSO-d6)：δ 0.91(t，3 H)，1.51-1.63(m，2 H)，3.16-3.22(m，2 H)，7.10-7.16(m，2 H)，7.22-7.28(m，2 H)，7.41-7.55(m，4 H)，7.74-7.85(m，2 H)，8.08(d，1 H)，8.23(s，1 H)，8.56-8.62(m，4 H)，9.18(s，1 H)。 Purity (UPLC-MS/ELSD): 76% (holding time: 0.74 minutes); MASS (ESI, Pos.): 558 (M+H) + ; 1 H-NMR (DMSO-d 6 ): δ 0.91 (t , 3 H), 1.51-1.63 (m, 2 H), 3.16-3.22 (m, 2 H), 7.10-7.16 (m, 2 H), 7.22-7.28 (m, 2 H), 7.41-7.55 (m , 4 H), 7.74-7.85 (m, 2 H), 8.08 (d, 1 H), 8.23 (s, 1 H), 8.56-8.62 (m, 4 H), 9.18 (s, 1 H).

實施例85-193：1-(6-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)-3-[2-(1H-吡唑-1-基)-5-(三氟甲基)苯基]脲 Example 85-193: 1-(6-{4-[2-(propylamino)-1,3-thiazol-5-yl]phenoxy}-3-pyridyl)-3-[2-(1H -pyrazol-1-yl)-5-(trifluoromethyl)phenyl]urea

純度(UPLC-MS/ELSD)：99%(保持時間：0.95分鐘)；MASS(ESI，Pos.)：580(M+H)+；1H-NMR(DMSO-d6)：δ 0.91(t，3 H)，1.51-1.63(m，2 H)，3.15-3.22 (m，2 H)，6.66-6.68(m，1 H)，6.98-7.06(m，3 H)，7.39-7.44(m，3 H)，7.50(dd，1 H)，7.71-7.76(m，2 H)，7.94(d，1 H)，7.99(dd，1 H)，8.15(d，1 H)，8.40(d，1 H)，8.60(s，1 H)，9.54(s，1 H)，9.80(s，1 H)。 Purity (UPLC-MS/ELSD): 99% (holding time: 0.95 minutes); MASS (ESI, Pos.): 580 (M+H) + ; 1 H-NMR (DMSO-d 6 ): δ 0.91 (t , 3 H), 1.51-1.63 (m, 2 H), 3.15-3.22 (m, 2 H), 6.66-6.68 (m, 1 H), 6.98-7.06 (m, 3 H), 7.39-7.44 (m , 3 H), 7.50 (dd, 1 H), 7.71-7.76 (m, 2 H), 7.94 (d, 1 H), 7.99 (dd, 1 H), 8.15 (d, 1 H), 8.40 (d) , 1 H), 8.60 (s, 1 H), 9.54 (s, 1 H), 9.80 (s, 1 H).

實施例85-194：1-(6-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)-3-{5-(三氟甲基)-2-[3-(三氟甲基)-1H-吡唑-1-基]苯基}脲 Example 85-194: 1-(6-{4-[2-(propylamino)-1,3-thiazol-5-yl]phenoxy}-3-pyridyl)-3-{5-(three Fluoromethyl)-2-[3-(trifluoromethyl)-1H-pyrazol-1-yl]phenyl}urea

純度(UPLC-MS/ELSD)：99%(保持時間：1.02分鐘)；MASS(ESI，Pos.)：648(M+H)+；1H-NMR(DMSO-d6)：δ 0.91(t，3 H)，1.51-1.63(m，2 H)，3.15-3.22(m，2 H)，6.98-7.05(m，3 H)，7.13(d，1 H)，7.39-7.43(m，3 H)，7.55(dd，1 H)，7.68(d，1 H)，7.74(t，1 H)，7.96(dd，1 H)，8.10(d，1 H)，8.43(s，1 H)，8.46-8.48(m，1 H)，8.52(d，1 H)，9.38(s，1 H)。 Purity (UPLC-MS/ELSD): 99% (holding time: 1.02 minutes); MASS (ESI, Pos.): 648 (M+H) + ; 1 H-NMR (DMSO-d 6 ): δ 0.91 (t , 3 H), 1.51-1.63 (m, 2 H), 3.15-3.22 (m, 2 H), 6.98-7.05 (m, 3 H), 7.13 (d, 1 H), 7.39-7.43 (m, 3) H), 7.55 (dd, 1 H), 7.68 (d, 1 H), 7.74 (t, 1 H), 7.96 (dd, 1 H), 8.10 (d, 1 H), 8.43 (s, 1 H) , 8.46-8.48 (m, 1 H), 8.52 (d, 1 H), 9.38 (s, 1 H).

實施例85-195：1-[2-(1-甲基-1H-吡唑-5-基)-5-(三氟甲基)苯基]-3-(6-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)脲 Example 85-195: 1-[2-(1-Methyl-1H-pyrazol-5-yl)-5-(trifluoromethyl)phenyl]-3-(6-{4-[2- (propylamino)-1,3-thiazol-5-yl]phenoxy}-3-pyridyl)urea

純度(UPLC-MS/ELSD)：99%(保持時間：0.93分鐘)；MASS(ESI，Pos.)：594(M+H)+；1H-NMR(DMSO-d6)：δ 0.91(t，3 H)，1.51-1.63(m，2 H)，3.15-3.22(m，2 H)，3.65(s，3 H)，6.45(d，1 H)，6.98-7.06(m，3 H)，7.39-7.50(m，5 H)，7.62(d，1 H)，7.74(t，1 H)，7.96-8.01(m，2 H)，8.10(d，1 H)，8.59(s，1 H)，9.41(s，1 H)。 Purity (UPLC-MS/ELSD): 99% (holding time: 0.93 minutes); MASS (ESI, Pos.): 594 (M+H) + ; 1 H-NMR (DMSO-d 6 ): δ 0.91 (t , 3 H), 1.51-1.63 (m, 2 H), 3.15-3.22 (m, 2 H), 3.65 (s, 3 H), 6.45 (d, 1 H), 6.98-7.06 (m, 3 H) , 7.39-7.50 (m, 5 H), 7.62 (d, 1 H), 7.74 (t, 1 H), 7.96-8.01 (m, 2 H), 8.10 (d, 1 H), 8.59 (s, 1) H), 9.41 (s, 1 H).

實施例85-196：1-[2-(3-甲基-1H-吡唑-1-基)-5-(三氟甲基)苯基]-3-(6-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)脲 Example 85-196: 1-[2-(3-Methyl-1H-pyrazol-1-yl)-5-(trifluoromethyl)phenyl]-3-(6-{4-[2- (propylamino)-1,3-thiazol-5-yl]phenoxy}-3-pyridyl)urea

純度(UPLC-MS/ELSD)：100%(保持時間：0.99分鐘)；MASS(ESI，Pos.)：594(M+H)+；1H-NMR(DMSO-d6)：δ 0.91(t，3 H)，1.51-1.63(m，2 H)，2.36(s，3 H)，3.16-3.22(m，2 H)，6.45(d，1 H)，6.99-7.06(m，3 H)，7.39-7.48(m，4 H)，7.68(d，1 H)，7.74(t，1 H)，7.97(dd，1 H)，8.16(d，1 H)，8.26(d，1 H)，8.58(s，1 H)，9.66(s，1 H)，9.76(s，1 H)。 Purity (UPLC-MS/ELSD): 100% (holding time: 0.99 minutes); MASS (ESI, Pos.): 594 (M+H) + ; 1 H-NMR (DMSO-d 6 ): δ 0.91 (t , 3 H), 1.51-1.63 (m, 2 H), 2.36 (s, 3 H), 3.16-3.22 (m, 2 H), 6.45 (d, 1 H), 6.99-7.06 (m, 3 H) , 7.39-7.48 (m, 4 H), 7.68 (d, 1 H), 7.74 (t, 1 H), 7.97 (dd, 1 H), 8.16 (d, 1 H), 8.26 (d, 1 H) , 8.58 (s, 1 H), 9.66 (s, 1 H), 9.76 (s, 1 H).

實施例85-197：1-[2-(4-甲基-1H-吡唑-1-基)-5-(三氟甲基)苯基]-3-(6-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)脲 Example 85-197: 1-[2-(4-Methyl-1H-pyrazol-1-yl)-5-(trifluoromethyl)phenyl]-3-(6-{4-[2- (propylamino)-1,3-thiazol-5-yl]phenoxy}-3-pyridyl)urea

純度(UPLC-MS/ELSD)：99%(保持時間：1.01分鐘)；MASS(ESI，Pos.)：594(M+H)+；1H-NMR(DMSO-d6)：δ 0.91(t，3 H)，1.51-1.63(m，2 H)，2.14(s，3 H)，3.16-3.22(m，2 H)，6.98-7.06(m，3 H)，7.39-7.49(m，4 H)，7.68(d，1 H)，7.72-7.77(m，2 H)，7.99(dd，1 H)，8.15-8.17(m，2 H)，8.59(s，1 H)，9.67(s，1 H)，9.81(s，1 H)。 Purity (UPLC-MS/ELSD): 99% (holding time: 1.01 minutes); MASS (ESI, Pos.): 594 (M+H) + ; 1 H-NMR (DMSO-d 6 ): δ 0.91 (t , 3 H), 1.51-1.63 (m, 2 H), 2.14 (s, 3 H), 3.16-3.22 (m, 2 H), 6.98-7.06 (m, 3 H), 7.39-7.49 (m, 4 H), 7.68 (d, 1 H), 7.72-7.77 (m, 2 H), 7.99 (dd, 1 H), 8.15-8.17 (m, 2 H), 8.59 (s, 1 H), 9.67 (s) , 1 H), 9.81 (s, 1 H).

實施例85-198：1-(6-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)-3-[2-(1H-吡唑-1-基)-4-(三氟甲基)苯基]脲 Example 85-198: 1-(6-{4-[2-(propylamino)-1,3-thiazol-5-yl]phenoxy}-3-pyridyl)-3-[2-(1H -pyrazol-1-yl)-4-(trifluoromethyl)phenyl]urea

純度(UPLC-MS/ELSD)：98%(保持時間：0.97分鐘)；MASS(ESI，Pos.)：580(M+H)+；1H-NMR(DMSO-d6)：δ 0.91(t，3 H)，1.51-1.63(m，2 H)，3.15-3.22(m，2 H)，6.65(t，1 H)，6.99-7.07(m，3 H)，7.39-7.45(m，3 H)，7.72-7.75(m，2 H)，7.81(d，1 H)，7.92(d，1 H)，7.96(dd，1 H)，8.17(d，1 H)，8.41-8.44(m，2 H)，9.40(s，1 H)，9.81(s，1 H)。 Purity (UPLC-MS/ELSD): 98% (holding time: 0.97 minutes); MASS (ESI, Pos.): 580 (M+H) + ; 1 H-NMR (DMSO-d 6 ): δ 0.91 (t , 3 H), 1.51-1.63 (m, 2 H), 3.15-3.22 (m, 2 H), 6.65 (t, 1 H), 6.99-7.07 (m, 3 H), 7.39-7.45 (m, 3) H), 7.72-7.75 (m, 2 H), 7.81 (d, 1 H), 7.92 (d, 1 H), 7.96 (dd, 1 H), 8.17 (d, 1 H), 8.41-8.44 (m) , 2 H), 9.40 (s, 1 H), 9.81 (s, 1 H).

實施例85-199：1-(6-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)-3-[2-(3-吡啶基)-4-(三氟甲基)苯基]脲 Example 85-199: 1-(6-{4-[2-(propylamino)-1,3-thiazol-5-yl]phenoxy}-3-pyridyl)-3-[2-(3 -pyridyl)-4-(trifluoromethyl)phenyl]urea

純度(UPLC-MS/ELSD)：96%(保持時間：0.87分鐘)；MASS(ESI，Pos.)：591(M+H)+；1H-NMR(DMSO-d6)：δ 0.91(t，3 H)，1.51-1.63(m，2 H)，3.15-3.22(m，2 H)，6.97-7.06(m，3 H)，7.39-7.44(m，3 H)，7.53-7.58(m，2 H)，7.72-7.76(m，2 H)，7.88-7.96(m，2 H)，8.09-8.10(m，2 H)，8.29(d，1 H)，8.64-8.69(m，2 H)，9.19(s，1 H)。 Purity (UPLC-MS/ELSD): 96% (holding time: 0.87 minutes); MASS (ESI, Pos.): 591 (M+H) + ; 1 H-NMR (DMSO-d 6 ): δ 0.91 (t , 3 H), 1.51-1.63 (m, 2 H), 3.15-3.22 (m, 2 H), 6.97-7.06 (m, 3 H), 7.39-7.44 (m, 3 H), 7.53-7.58 (m , 2 H), 7.72-7.76 (m, 2 H), 7.88-7.96 (m, 2 H), 8.09-8.10 (m, 2 H), 8.29 (d, 1 H), 8.64-8.69 (m, 2) H), 9.19 (s, 1 H).

實施例85-200：1-[5-氯-2-(1H-吡唑-1-基)苯基]-3-(6-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)脲 Example 85-200: 1-[5-Chloro-2-(1H-pyrazol-1-yl)phenyl]-3-(6-{4-[2-(propylamino)-1,3-thiazole -5-yl]phenoxy}-3-pyridyl)urea

純度(UPLC-MS/ELSD)：97%(保持時間：0.93分鐘)；MASS(ESI，Pos.)：547(M+H)+；1H-NMR(DMSO-d6)：δ 0.91(t，3 H)，1.51-1.63(m，2 H)，3.15-3.22(m，2 H)，6.61-6.62(m，1 H)，6.98-7.07(m，3 H)，7.20(dd，1 H)，7.39-7.43(m，3 H)，7.49(d，1 H)，7.74(t，1 H)，7.89(d，1 H)，7.96(dd，1 H)，8.15(d，1 H)，8.26-8.29(m，2 H)，9.21(s，1 H)，9.73(s，1 H)。 Purity (UPLC-MS/ELSD): 97% (holding time: 0.93 minutes); MASS (ESI, Pos.): 547 (M+H) + ; 1 H-NMR (DMSO-d 6 ): δ 0.91 (t , 3 H), 1.51-1.63 (m, 2 H), 3.15-3.22 (m, 2 H), 6.61-6.62 (m, 1 H), 6.98-7.07 (m, 3 H), 7.20 (dd, 1 H), 7.39-7.43 (m, 3 H), 7.49 (d, 1 H), 7.74 (t, 1 H), 7.89 (d, 1 H), 7.96 (dd, 1 H), 8.15 (d, 1) H), 8.26-8.29 (m, 2 H), 9.21 (s, 1 H), 9.73 (s, 1 H).

實施例85-201：1-[5-氯-2-(3-吡啶基)苯基]-3-(6-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)脲 Example 85-201:1-[5-Chloro-2-(3-pyridyl)phenyl]-3-(6-{4-[2-(propylamino)-1,3-thiazol-5-yl Phenoxy}-3-pyridyl)urea

純度(UPLC-MS/ELSD)：98%(保持時間：0.81分鐘)；MASS(ESI，Pos.)：557(M+H)+；1H-NMR(DMSO-d6)：δ 0.91(t，3 H)，1.51-1.63(m，2 H)，3.15-3.22(m，2 H)，6.97-7.06(m，3 H)，7.19-7.28(m，2 H)，7.38-7.43(m，3 H)，7.54(dd，1 H)，7.74(t，1 H)，7.81-7.85(m，1 H)，7.92-7.97(m，2 H)，8.08(d，1 H)，8.10(d，1 H)，8.59(dd，1 H)，8.64(dd，1 H)，9.11(s，1 H)。 Purity (UPLC-MS/ELSD): 98% (holding time: 0.81 minutes); MASS (ESI, Pos.): 557 (M+H) + ; 1 H-NMR (DMSO-d 6 ): δ 0.91 (t , 3 H), 1.51-1.63 (m, 2 H), 3.15-3.22 (m, 2 H), 6.97-7.06 (m, 3 H), 7.19-7.28 (m, 2 H), 7.38-7.43 (m , 3 H), 7.54 (dd, 1 H), 7.74 (t, 1 H), 7.81-7.85 (m, 1 H), 7.92-7.97 (m, 2 H), 8.08 (d, 1 H), 8.10 (d, 1 H), 8.59 (dd, 1 H), 8.64 (dd, 1 H), 9.11 (s, 1 H).

實施例85-202：1-(2-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-(2H-1，2，3-三唑-2-基)-5-(三氟甲基)苯基]脲 Example 85-202: 1-(2-{4-[2-(propylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-[2-(2H -1,2,3-triazol-2-yl)-5-(trifluoromethyl)phenyl]urea

純度(UPLC-MS/ELSD)：100%(保持時間：0.93分鐘)；MASS(ESI，Pos.)：582(M+H)+；1H-NMR(DMSO-d6)：δ 0.91(t，3 H)，1.51-1.63(m，2 H)，3.16-3.22(m，2 H)，7.12-7.16(m，2 H)，7.41-7.46(m，3 H)，7.58(dd，1 H)，7.76(t，1 H)，8.06(d，1 H)，8.32(s，2 H)，8.65-8.69(m，3 H)，9.66(s，1 H)，10.0(s，1 H)。 Purity (UPLC-MS/ELSD): 100% (holding time: 0.93 minutes); MASS (ESI, Pos.): 582 (M+H) + ; 1 H-NMR (DMSO-d 6 ): δ 0.91 (t , 3 H), 1.51-1.63 (m, 2 H), 3.16-3.22 (m, 2 H), 7.12-7.16 (m, 2 H), 7.41-7.46 (m, 3 H), 7.58 (dd, 1 H), 7.76 (t, 1 H), 8.06 (d, 1 H), 8.32 (s, 2 H), 8.65-8.69 (m, 3 H), 9.66 (s, 1 H), 10.0 (s, 1) H).

實施例85-203：1-[5-氯-2-(1H-1，2，3-三唑-1-基)苯基]-3-(2-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 85-203: 1-[5-Chloro-2-(1H-1,2,3-triazol-1-yl)phenyl]-3-(2-{4-[2-(propylamino) -1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

純度(UPLC-MS/ELSD)：100%(保持時間：0.80分鐘)；MASS(ESI，Pos.)：548(M+H)+；1H-NMR(DMSO-d6)：δ 0.91(t，3 H)，1.51-1.63(m，2 H)，3.16-3.22(m，2 H)，7.11-7.15(m，2 H)，7.32(dd，1 H)，7.42-7.52(m，4 H)，7.76(t，1 H)，8.06(d，1 H)，8.27(d，1 H)，8.49(s，1 H)，8.59(d，1 H)，8.64(s，2 H)，9.57(s，1 H)。 Purity (UPLC-MS/ELSD): 100% (holding time: 0.80 minutes); MASS (ESI, Pos.): 548 (M+H) + ; 1 H-NMR (DMSO-d 6 ): δ 0.91 (t , 3 H), 1.51-1.63 (m, 2 H), 3.16-3.22 (m, 2 H), 7.11-7.15 (m, 2 H), 7.32 (dd, 1 H), 7.42-7.52 (m, 4) H), 7.76 (t, 1 H), 8.06 (d, 1 H), 8.27 (d, 1 H), 8.49 (s, 1 H), 8.59 (d, 1 H), 8.64 (s, 2 H) , 9.57 (s, 1 H).

實施例85-204：1-[5-氯-2-(2H-1，2，3-三唑-2-基)苯基]-3-(2-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 85-204: 1-[5-Chloro-2-(2H-1,2,3-triazol-2-yl)phenyl]-3-(2-{4-[2-(propylamino) -1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

純度(UPLC-MS/ELSD)：100%(保持時間：0.90分鐘)；MASS(ESI，Pos.)：548(M+H)+；1H-NMR(DMSO-d6)：δ 0.91(t，3 H)，1.51-1.63(m，2 H)，3.16-3.22(m，2 H)，7.12-7.16(m，2 H)，7.28(dd，1 H)，7.42-7.46(m，3 H)，7.74-7.81(m，2 H)，8.26(s，2 H)，8.32(d，1 H)，8.68(s，2 H)，9.35(s，1 H)，9.91(s，1 H)。 Purity (UPLC-MS/ELSD): 100% (holding time: 0.90 minutes); MASS (ESI, Pos.): 548 (M+H) + ; 1 H-NMR (DMSO-d 6 ): δ 0.91 (t , 3 H), 1.51-1.63 (m, 2 H), 3.16-3.22 (m, 2 H), 7.12-7.16 (m, 2 H), 7.28 (dd, 1 H), 7.42-7.46 (m, 3) H), 7.74-7.81 (m, 2 H), 8.26 (s, 2 H), 8.32 (d, 1 H), 8.68 (s, 2 H), 9.35 (s, 1 H), 9.91 (s, 1) H).

實施例85-205：1-[2-氟-5-(三氟甲基)苯基]-3-(2-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 85-205: 1-[2-Fluoro-5-(trifluoromethyl)phenyl]-3-(2-{4-[2-(propylamino)-1,3-thiazol-5-yl Phenoxy}-5-pyrimidinyl)urea

純度(UPLC-MS/ELSD)：100%(保持時間：0.89分鐘)；MASS(ESI，Pos.)：533(M+H)+；1H-NMR(DMSO-d6)：δ 0.91(t，3 H)，1.51-1.63(m，2 H)，3.16-3.22(m，2 H)，7.12-7.16(m，2 H)，7.38-7.53(m，5 H)，7.76(t，1 H)，8.52(dd，1 H)，8.71(s，2 H)，9.09(s，1 H)，9.28(s，1 H)。 Purity (UPLC-MS/ELSD): 100% (holding time: 0.89 minutes); MASS (ESI, Pos.): 533 (M+H) + ; 1 H-NMR (DMSO-d 6 ): δ 0.91 (t , 3 H), 1.51-1.63 (m, 2 H), 3.16-3.22 (m, 2 H), 7.12-7.16 (m, 2 H), 7.38-7.53 (m, 5 H), 7.76 (t, 1 H), 8.52 (dd, 1 H), 8.71 (s, 2 H), 9.09 (s, 1 H), 9.28 (s, 1 H).

實施例85-206：1-[2-甲基-5-(三氟甲基)苯基]-3-(2-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 85-206: 1-[2-Methyl-5-(trifluoromethyl)phenyl]-3-(2-{4-[2-(propylamino)-1,3-thiazole-5- Phenyloxy-5-pyrimidinyl)urea

TLC：Rf 0.48(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 0.91(t，3 H)，1.51-1.63(m，2 H)，2.32(s，3 H)，3.16-3.23(m，2 H)，7.12-7.16(m，2 H)，7.29(d，1 H)，7.40-7.46(m，4 H)，7.76(t，1 H)，8.26(s，1 H)，8.37(s，1 H)，8.72(s，2 H)，9.32(s，1 H)。 TLC: Rf 0.48 (ethyl acetate); 1 H-NMR (DMSO -d 6): δ 0.91 (t, 3 H), 1.51-1.63 (m, 2 H), 2.32 (s, 3 H), 3.16- 3.23 (m, 2 H), 7.12-7.16 (m, 2 H), 7.29 (d, 1 H), 7.40-7.46 (m, 4 H), 7.76 (t, 1 H), 8.26 (s, 1 H) ), 8.37 (s, 1 H), 8.72 (s, 2 H), 9.32 (s, 1 H).

實施例85-207：1-(2，5-二氯苯基)-3-(2-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 85-207: 1-(2,5-Dichlorophenyl)-3-(2-{4-[2-(propylamino)-1,3-thiazol-5-yl]phenoxy}- 5-pyrimidinyl urea

純度(UPLC-MS/ELSD)：100%(保持時間：0.89分鐘)；MASS(ESI，Pos.)：515(M+H)+；1H-NMR(DMSO-d6)：δ 0.91(t，3 H)，1.51-1.63(m，2 H)，3.13-3.23(m，2 H)，7.10-7.18(m，2 H)，7.36-7.47(m，4 H)，7.63(d，1 H)， 7.71-7.81(m，1 H)，8.14(d，1 H)，8.59(s，1 H)，8.70(s，2 H)，9.58(s，1 H)。 Purity (UPLC-MS/ELSD): 100% (holding time: 0.89 minutes); MASS (ESI, Pos.): 515 (M+H) + ; 1 H-NMR (DMSO-d 6 ): δ 0.91 (t , 3 H), 1.51-1.63 (m, 2 H), 3.13 - 3.23 (m, 2 H), 7.10-7.18 (m, 2 H), 7.36-7.47 (m, 4 H), 7.63 (d, 1) H), 7.71-7.81 (m, 1 H), 8.14 (d, 1 H), 8.59 (s, 1 H), 8.70 (s, 2 H), 9.58 (s, 1 H).

實施例85-208：1-(2，4-二氯苯基)-3-(2-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 85-208: 1-(2,4-Dichlorophenyl)-3-(2-{4-[2-(propylamino)-1,3-thiazol-5-yl]phenoxy}- 5-pyrimidinyl urea

純度(UPLC-MS/ELSD)：99%(保持時間：0.90分鐘)；MASS(ESI，Pos.)：515(M+H)+；1H-NMR(DMSO-d6)：δ 0.91(t，3 H)，1.51-1.63(m，2 H)，3.16-3.23(m，2 H)，7.11-7.16(m，2 H)，7.36-7.47(m，4 H)，7.63(d，1 H)，7.76(t，1 H)，8.13(d，1 H)，8.57(s，1 H)，8.70(s，2 H)，9.57(s，1 H)。 Purity (UPLC-MS/ELSD): 99% (holding time: 0.90 minutes); MASS (ESI, Pos.): 515 (M+H) + ; 1 H-NMR (DMSO-d 6 ): δ 0.91 (t , 3 H), 1.51-1.63 (m, 2 H), 3.16-3.23 (m, 2 H), 7.11-7.16 (m, 2 H), 7.36-7.47 (m, 4 H), 7.63 (d, 1) H), 7.76 (t, 1 H), 8.13 (d, 1 H), 8.57 (s, 1 H), 8.70 (s, 2 H), 9.57 (s, 1 H).

實施例85-209：1-(2，5-二氟苯基)-3-(2-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 85-209: 1-(2,5-Difluorophenyl)-3-(2-{4-[2-(propylamino)-1,3-thiazol-5-yl]phenoxy}- 5-pyrimidinyl urea

純度(UPLC-MS/ELSD)：98%(保持時間：0.81分鐘)；MASS(ESI，Pos.)：483(M+H)+；1H-NMR(DMSO-d6)：δ 0.91(t，3 H)，1.51-1.63(m，2 H)，3.16-3.22(m，2 H)，6.80-6.89(m，1 H)，7.12-7.16(m，2 H)，7.26-7.34(m，1 H)，7.39-7.46(m，3 H)，7.76(t，1 H)，7.93-8.00(m，1 H)，8.70(s，2 H)，8.96(s，1 H)，9.26(s，1 H)。 Purity (UPLC-MS/ELSD): 98% (holding time: 0.81 minutes); MASS (ESI, Pos.): 483 (M+H) + ; 1 H-NMR (DMSO-d 6 ): δ 0.91 (t , 3 H), 1.51-1.63 (m, 2 H), 3.16-3.22 (m, 2 H), 6.80-6.89 (m, 1 H), 7.12-7.16 (m, 2 H), 7.26-7.34 (m , 1 H), 7.39-7.46 (m, 3 H), 7.76 (t, 1 H), 7.93-8.00 (m, 1 H), 8.70 (s, 2 H), 8.96 (s, 1 H), 9.26 (s, 1 H).

實施例85-210：1-[3-(二氟甲基)苯基]-3-(2-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 85-210: 1-[3-(Difluoromethyl)phenyl]-3-(2-{4-[2-(propylamino)-1,3-thiazol-5-yl]phenoxy }-5-pyrimidinyl)urea

純度(UPLC-MS/ELSD)：100%(保持時間：0.77分鐘)；MASS(ESI，Pos.)：497(M+H)+；1H-NMR(DMSO-d6)：δ 0.91(t，3 H)，1.51-1.63(m，2 H)，3.16-3.23(m，2 H)，6.81-7.18(m，4 H)，7.39-7.53(m，5 H)，7.74-7.76(m， 2 H)，8.70(s，2 H)，8.91(s，1 H)，9.17(s，1 H)。 Purity (UPLC-MS/ELSD): 100% (holding time: 0.77 minutes); MASS (ESI, Pos.): 497 (M+H) + ; 1 H-NMR (DMSO-d 6 ): δ 0.91 (t , 3 H), 1.51-1.63 (m, 2 H), 3.16-3.23 (m, 2 H), 6.81-7.18 (m, 4 H), 7.39-7.53 (m, 5 H), 7.74-7.76 (m) , 2 H), 8.70 (s, 2 H), 8.91 (s, 1 H), 9.17 (s, 1 H).

實施例85-211：1-[2-氯-5-(三氟甲基)苯基]-3-(6-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)脲 Example 85-211:1-[2-Chloro-5-(trifluoromethyl)phenyl]-3-(6-{4-[2-(propylamino)-1,3-thiazol-5-yl Phenoxy}-3-pyridyl)urea

純度(UPLC-MS/ELSD)：100%(保持時間：0.98分鐘)；MASS(ESI，Pos.)：548(M+H)+；1H-NMR(DMSO-d6)：δ 0.91(t，3 H)，1.51-1.63(m，2 H)，3.16-3.22(m，2 H)，7.01-7.08(m，3 H)，7.36-7.44(m，4 H)，7.70-7.76(m，2 H)，8.04(dd，1 H)，8.17(d，1 H)，8.60(d，1 H)，8.66(s，1 H)，9.63(s，1 H)。 Purity (UPLC-MS/ELSD): 100% (holding time: 0.98 minutes); MASS (ESI, Pos.): 548 (M+H) + ; 1 H-NMR (DMSO-d 6 ): δ 0.91 (t , 3 H), 1.51-1.63 (m, 2 H), 3.16-3.22 (m, 2 H), 7.01-7.08 (m, 3 H), 7.36-7.44 (m, 4 H), 7.70-7.76 (m , 2 H), 8.04 (dd, 1 H), 8.17 (d, 1 H), 8.60 (d, 1 H), 8.66 (s, 1 H), 9.63 (s, 1 H).

實施例85-212：1-[2-氟-5-(三氟甲基)苯基]-3-(6-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)脲 Example 85-212: 1-[2-Fluoro-5-(trifluoromethyl)phenyl]-3-(6-{4-[2-(propylamino)-1,3-thiazol-5-yl Phenoxy}-3-pyridyl)urea

純度(UPLC-MS/ELSD)：99%(保持時間：0.94分鐘)；MASS(ESI，Pos.)：532(M+H)+；1H-NMR(DMSO-d6)：δ 0.91(t，3 H)，1.51-1.63(m，2 H)，3.16-3.22(m，2 H)，7.01-7.07(m，3 H)，7.39-7.52(m，5 H)，7.74(t，1 H)，8.03(dd，1 H)，8.16(d，1 H)，8.56(dd，1 H)，8.95(d，1 H)，9.23(s，1 H)。 Purity (UPLC-MS/ELSD): 99% (holding time: 0.94 minutes); MASS (ESI, Pos.): 532 (M+H) + ; 1 H-NMR (DMSO-d 6 ): δ 0.91 (t , 3 H), 1.51-1.63 (m, 2 H), 3.16-3.22 (m, 2 H), 7.01-7.07 (m, 3 H), 7.39-7.52 (m, 5 H), 7.74 (t, 1) H), 8.03 (dd, 1 H), 8.16 (d, 1 H), 8.56 (dd, 1 H), 8.95 (d, 1 H), 9.23 (s, 1 H).

實施例85-213：1-[2-甲基-5-(三氟甲基)苯基]-3-(6-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)脲 Example 85-213: 1-[2-Methyl-5-(trifluoromethyl)phenyl]-3-(6-{4-[2-(propylamino)-1,3-thiazole-5- Phenoxy}-3-pyridyl)urea

純度(UPLC-MS/ELSD)：98%(保持時間：0.95分鐘)；MASS(ESI，Pos.)：528(M+H)+；1H-NMR(DMSO-d6)：δ 0.91(t，3 H)，1.51-1.63(m，2 H)，2.31(s，3 H)，3.15-3.22(m，2 H)，7.00-7.07(m，3 H)，7.26(d，1 H)，7.39-7.44(m，4 H)，7.74(t，1 H)，8.04(dd，1 H)，8.16(d，1 H)，8.23(s， 1 H)，8.31(s，1 H)，9.26(s，1 H)。 Purity (UPLC-MS/ELSD): 98% (holding time: 0.95 minutes); MASS (ESI, Pos.): 528 (M+H) + ; 1 H-NMR (DMSO-d 6 ): δ 0.91 (t , 3 H), 1.51-1.63 (m, 2 H), 2.31 (s, 3 H), 3.15-3.22 (m, 2 H), 7.00-7.07 (m, 3 H), 7.26 (d, 1 H) , 7.39-7.44 (m, 4 H), 7.74 (t, 1 H), 8.04 (dd, 1 H), 8.16 (d, 1 H), 8.23 (s, 1 H), 8.31 (s, 1 H) , 9.26 (s, 1 H).

實施例85-214：1-(2，5-二氯苯基)-3-(6-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)脲 Example 85-214: 1-(2,5-Dichlorophenyl)-3-(6-{4-[2-(propylamino)-1,3-thiazol-5-yl]phenoxy}- 3-pyridyl)urea

純度(UPLC-MS/ELSD)：100%(保持時間：0.96分鐘)；MASS(ESI，Pos.)：514(M+H)+；1H-NMR(DMSO-d6)：δ 0.91(t，3 H)，1.51-1.63(m，2 H)，3.15-3.22(m，2 H)，7.01-7.11(m，4 H)，7.39-7.48(m，4 H)，7.74(t，1 H)，8.01(dd，1 H)，8.17(d，1 H)，8.29(d，1 H)，8.51(s，1 H)，9.59(s，1 H)。 Purity (UPLC-MS/ELSD): 100% (holding time: 0.96 minutes); MASS (ESI, Pos.): 514 (M+H) + ; 1 H-NMR (DMSO-d 6 ): δ 0.91 (t , 3 H), 1.51-1.63 (m, 2 H), 3.15-3.22 (m, 2 H), 7.01-7.11 (m, 4 H), 7.39-7.48 (m, 4 H), 7.74 (t, 1 H), 8.01 (dd, 1 H), 8.17 (d, 1 H), 8.29 (d, 1 H), 8.51 (s, 1 H), 9.59 (s, 1 H).

實施例85-215：1-(2，4-二氯苯基)-3-(6-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)脲 Example 85-215: 1-(2,4-Dichlorophenyl)-3-(6-{4-[2-(propylamino)-1,3-thiazol-5-yl]phenoxy}- 3-pyridyl)urea

純度(UPLC-MS/ELSD)：100%(保持時間：0.93分鐘)；MASS(ESI，Pos.)：514(M+H)+；1H-NMR(DMSO-d6)：δ 0.91(t，3 H)，1.51-1.63(m，2 H)，3.15-3.22(m，2 H)，7.00-7.07(m，3 H)，7.36-7.44(m，4 H)，7.62(d，1 H)，7.74(t，1 H)，8.00(dd，1 H)，8.17-8.18(m，2 H)，8.44(s，1 H)，9.51(s，1 H)。 Purity (UPLC-MS/ELSD): 100% (holding time: 0.93 minutes); MASS (ESI, Pos.): 514 (M+H) + ; 1 H-NMR (DMSO-d 6 ): δ 0.91 (t , 3 H), 1.51-1.63 (m, 2 H), 3.15-3.22 (m, 2 H), 7.00-7.07 (m, 3 H), 7.36-7.44 (m, 4 H), 7.62 (d, 1) H), 7.74 (t, 1 H), 8.00 (dd, 1 H), 8.17-8.18 (m, 2 H), 8.44 (s, 1 H), 9.51 (s, 1 H).

實施例85-216：1-(2，5-二氟苯基)-3-(6-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)脲 Example 85-216: 1-(2,5-Difluorophenyl)-3-(6-{4-[2-(propylamino)-1,3-thiazol-5-yl]phenoxy}- 3-pyridyl)urea

純度(UPLC-MS/ELSD)：99%(保持時間：0.88分鐘)；MASS(ESI，Pos.)：482(M+H)+；1H-NMR(DMSO-d6)：δ 0.91(t，3 H)，1.51-1.63(m，2 H)，3.15-3.22(m，2 H)，6.78-6.86(m，1 H)，7.01-7.07(m，3 H)，7.24-7.33(m，1 H)，7.39-7.44(m，3 H)，7.74(t，1 H)，7.96-8.03(m，2 H)，8.16 (d，1 H)，8.82(s，1 H)，9.20(s，1 H)。 Purity (UPLC-MS/ELSD): 99% (holding time: 0.88 minutes); MASS (ESI, Pos.): 482 (M+H) + ; 1 H-NMR (DMSO-d 6 ): δ 0.91 (t , 3 H), 1.51-1.63 (m, 2 H), 3.15-3.22 (m, 2 H), 6.78-6.86 (m, 1 H), 7.01-7.07 (m, 3 H), 7.24-7.33 (m , 1 H), 7.39-7.44 (m, 3 H), 7.74 (t, 1 H), 7.96-8.03 (m, 2 H), 8.16 (d, 1 H), 8.82 (s, 1 H), 9.20 (s, 1 H).

實施例85-217：1-[3-(二氟甲基)苯基]-3-(6-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)脲 Example 85-217: 1-[3-(Difluoromethyl)phenyl]-3-(6-{4-[2-(propylamino)-1,3-thiazol-5-yl]phenoxy }-3-pyridyl)urea

純度(UPLC-MS/ELSD)：100%(保持時間：0.82分鐘)；MASS(ESI，Pos.)：496(M+H)+；1H-NMR(DMSO-d6)：δ 0.91(t，3 H)，1.51-1.63(m，2 H)，3.15-3.22(m，2 H)，6.81-7.18(m，5 H)，7.39-7.51(m，5 H)，7.72-7.77(m，2 H)，7.90(dd，1 H)，8.19(dd，1 H)，8.81(s，1 H)，8.99(s，1 H)。 Purity (UPLC-MS/ELSD): 100% (holding time: 0.82 minutes); MASS (ESI, Pos.): 496 (M+H) + ; 1 H-NMR (DMSO-d 6 ): δ 0.91 (t , 3 H), 1.51-1.63 (m, 2 H), 3.15-3.22 (m, 2 H), 6.81-7.18 (m, 5 H), 7.39-7.51 (m, 5 H), 7.72-7.77 (m , 2 H), 7.90 (dd, 1 H), 8.19 (dd, 1 H), 8.81 (s, 1 H), 8.99 (s, 1 H).

實施例85-218：1-[2-氯-4-(三氟甲基)苯基]-3-(6-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)脲 Example 85-218: 1-[2-Chloro-4-(trifluoromethyl)phenyl]-3-(6-{4-[2-(propylamino)-1,3-thiazol-5-yl Phenoxy}-3-pyridyl)urea

純度(UPLC-MS/ELSD)：100%(保持時間：1.00分鐘)；MASS(ESI，Pos.)：548(M+H)+；1H-NMR(DMSO-d6)：δ 0.91(t，3 H)，1.51-1.63(m，2 H)，3.15-3.22(m，2 H)，7.02-7.09(m，3 H)，7.39-7.44(m，3 H)，7.68(dd，1 H)，7.74(t，1 H)，7.87(d，1 H)，8.02(dd，1 H)，8.19(d，1 H)，8.44(d，1 H)，8.67(s，1 H)，9.68(s，1 H)。 Purity (UPLC-MS/ELSD): 100% (holding time: 1.00 minutes); MASS (ESI, Pos.): 548 (M+H) + ; 1 H-NMR (DMSO-d 6 ): δ 0.91 (t , 3 H), 1.51-1.63 (m, 2 H), 3.15-3.22 (m, 2 H), 7.02-7.09 (m, 3 H), 7.39-7.44 (m, 3 H), 7.68 (dd, 1 H), 7.74 (t, 1 H), 7.87 (d, 1 H), 8.02 (dd, 1 H), 8.19 (d, 1 H), 8.44 (d, 1 H), 8.67 (s, 1 H) , 9.68 (s, 1 H).

實施例85-219：1-(6-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)-3-[2-(2H-1，2，3-三唑-2-基)-5-(三氟甲基)苯基]脲 Example 85-219: 1-(6-{4-[2-(propylamino)-1,3-thiazol-5-yl]phenoxy}-3-pyridyl)-3-[2-(2H -1,2,3-triazol-2-yl)-5-(trifluoromethyl)phenyl]urea

純度(UPLC-MS/ELSD)：100%(保持時間：0.98分鐘)；MASS(ESI，Pos.)：581(M+H)+；1H-NMR(DMSO-d6)：δ 0.91(t，3 H)，1.51-1.63(m，2 H)，3.15-3.22(m，2 H)，7.00-7.07(m，3 H)，7.39-7.44(m，3 H)，7.56(dd，1 H)，7.74(t，1 H)，7.99-8.06(m，2 H)，8.16(d，1 H)，8.32(s，2 H)，8.67(s，1 H)，9.54(s，1 H)，9.87(s，1 H)。 Purity (UPLC-MS/ELSD): 100% (holding time: 0.98 minutes); MASS (ESI, Pos.): 581 (M+H) + ; 1 H-NMR (DMSO-d 6 ): δ 0.91 (t , 3 H), 1.51-1.63 (m, 2 H), 3.15-3.22 (m, 2 H), 7.00-7.07 (m, 3 H), 7.39-7.44 (m, 3 H), 7.56 (dd, 1 H), 7.74 (t, 1 H), 7.99-8.06 (m, 2 H), 8.16 (d, 1 H), 8.32 (s, 2 H), 8.67 (s, 1 H), 9.54 (s, 1) H), 9.87 (s, 1 H).

實施例85-220：1-[5-氯-2-(1H-1，2，3-三唑-1-基)苯基]-3-(6-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)脲 Example 85-220: 1-[5-Chloro-2-(1H-1,2,3-triazol-1-yl)phenyl]-3-(6-{4-[2-(propylamino) -1,3-thiazol-5-yl]phenoxy}-3-pyridyl)urea

純度(UPLC-MS/ELSD)：99%(保持時間：0.86分鐘)；MASS(ESI，Pos.)：547(M+H)+；1H-NMR(DMSO-d6)：δ 0.90(t，3 H)，1.50-1.62(m，2 H)，3.15-3.21(m，2 H)，6.97-7.05(m，3 H)，7.29(dd，1 H)，7.38-7.49(m，4 H)，7.73(t，1 H)，7.94(dd，1 H)，8.05(d，1 H)，8.10(d，1 H)，8.28(d，1 H)，8.34(s，1 H)，8.58(d，1 H)，9.47(s，1 H)。 Purity (UPLC-MS/ELSD): 99% (holding time: 0.86 minutes); MASS (ESI, Pos.): 547 (M+H) + ; 1 H-NMR (DMSO-d 6 ): δ 0.90 (t , 3 H), 1.50-1.62 (m, 2 H), 3.15-3.21 (m, 2 H), 6.97-7.05 (m, 3 H), 7.29 (dd, 1 H), 7.38-7.49 (m, 4) H), 7.73 (t, 1 H), 7.94 (dd, 1 H), 8.05 (d, 1 H), 8.10 (d, 1 H), 8.28 (d, 1 H), 8.34 (s, 1 H) , 8.58 (d, 1 H), 9.47 (s, 1 H).

實施例85-221：1-[5-氯-2-(2H-1，2，3-三唑-2-基)苯基]-3-(6-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-3-吡啶基)脲 Example 85-221:1-[5-Chloro-2-(2H-1,2,3-triazol-2-yl)phenyl]-3-(6-{4-[2-(propylamino) -1,3-thiazol-5-yl]phenoxy}-3-pyridyl)urea

純度(UPLC-MS/ELSD)：100%(保持時間：0.93分鐘)；MASS(ESI，Pos.)：547(M+H)+；1H-NMR(DMSO-d6)：δ 0.91(t，3 H)，1.51-1.63(m，2 H)，3.15-3.22(m，2 H)，6.99-7.10(m，3 H)，7.27(dd，1 H)，7.39-7.45(m，3 H)，7.72-7.79(m，2 H)，7.98(dd，1 H)，8.15(d，1 H)，8.25(s，2 H)，8.33(d，1 H)，9.24(s，1 H)，9.77(s，1 H)。 Purity (UPLC-MS/ELSD): 100% (holding time: 0.93 minutes); MASS (ESI, Pos.): 547 (M+H) + ; 1 H-NMR (DMSO-d 6 ): δ 0.91 (t , 3 H), 1.51-1.63 (m, 2 H), 3.15-3.22 (m, 2 H), 6.99-7.10 (m, 3 H), 7.27 (dd, 1 H), 7.39-7.45 (m, 3) H), 7.72-7.79 (m, 2 H), 7.98 (dd, 1 H), 8.15 (d, 1 H), 8.25 (s, 2 H), 8.33 (d, 1 H), 9.24 (s, 1) H), 9.77 (s, 1 H).

實施例85-222：1-(3，5-二氟苯基)-3-(2-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 85-222: 1-(3,5-Difluorophenyl)-3-(2-{4-[2-(propylamino)-1,3-thiazol-5-yl]phenoxy}- 5-pyrimidinyl urea

純度(UPLC-MS/ELSD)：100%(保持時間：0.80分鐘)；MASS(ESI，Pos.)：483(M+H)+；1H-NMR(DMSO-d6)：δ 0.91(t，3 H)，1.51-1.63(m，2 H)，3.16-3.22(m，2 H)，6.77-6.86(m，1 H)，7.13-7.20(m，4 H)，7.42-7.46(m，3 H)，7.76(t，1 H)，8.69(s，2 H)，9.01(s，1 H)，9.35(s，1 H)。 Purity (UPLC-MS/ELSD): 100% (holding time: 0.80 minutes); MASS (ESI, Pos.): 483 (M+H) + ; 1 H-NMR (DMSO-d 6 ): δ 0.91 (t , 3 H), 1.51-1.63 (m, 2 H), 3.16-3.22 (m, 2 H), 6.77-6.86 (m, 1 H), 7.13-7.20 (m, 4 H), 7.42-7.46 (m , 3 H), 7.76 (t, 1 H), 8.69 (s, 2 H), 9.01 (s, 1 H), 9.35 (s, 1 H).

實施例85-223：1-{2-[3-(二氟甲基)-1H-吡唑-1-基]-5-(三氟 甲基)苯基}-3-(2-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Examples 85-223: 1-{2-[3-(Difluoromethyl)-1H-pyrazol-1-yl]-5-(trifluoro Methyl)phenyl}-3-(2-{4-[2-(propylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.79(己烷：乙酸乙酯=1：2)；1H-NMR(DMSO-d6)：δ 0.91(t，3 H)，1.52-1.62(m，2 H)，3.16-3.22(m，2 H)，6.93(d，1 H)，6.99(dd，1 H)，7.13(d，2 H)，7.43(d，2 H)，7.43(s，1 H)，7.50(dd，1 H)，7.71-7.78(m，2 H)，8.44(d，1 H)，8.54(d，1 H)，8.66(s，2 H)，8.94(s，1 H)，9.65(s，1 H)。 TLC: Rf 0.79 (hexane: ethyl acetate = 1:2); 1 H-NMR (DMSO-d 6 ): δ 0.91 (t, 3 H), 1.52-1.62 (m, 2 H), 3.16-3.22 (m, 2 H), 6.93 (d, 1 H), 6.99 (dd, 1 H), 7.13 (d, 2 H), 7.43 (d, 2 H), 7.43 (s, 1 H), 7.50 (dd , 1 H), 7.71-7.78 (m, 2 H), 8.44 (d, 1 H), 8.54 (d, 1 H), 8.66 (s, 2 H), 8.94 (s, 1 H), 9.65 (s) , 1 H).

實施例85-224：1-[2-(4-{2-[3-(2-羥基-2-丙基)-2-側氧基-1-吡咯啶基]-1，3-噻唑-5-基}苯氧基)-5-嘧啶基]-3-[2-(甲基磺醯基)-5-(三氟甲基)苯基]脲 Example 85-224: 1-[2-(4-{2-[3-(2-hydroxy-2-propyl)-2-oxo-l-pyrrolidinyl]-1,3-thiazole- 5-yl}phenoxy)-5-pyrimidinyl]-3-[2-(methylsulfonyl)-5-(trifluoromethyl)phenyl]urea

TLC：Rf 0.30(甲醇：氯仿=1：19)；1H-NMR(DMSO-d6)：δ 1.27(d，6 H)，2.20-2.28(m，2 H)，2.28(t，1 H)，3.84-4.07(m，2 H)，4.65(s，1 H)，7.20-7.27(m，2 H)，7.61-7.70(m，3 H)，7.90(s，1 H)，8.06(d，1 H)，8.61-8.63(m，1 H)，8.73(s，2 H)，8.96(s，1 H)，10.3(s，1 H)。 TLC: Rf 0.30 (methanol: chloroform = 1:19); 1 H-NMR (DMSO-d 6 ): δ 1.27 (d, 6 H), 2.20-2.28 (m, 2 H), 2.28 (t, 1 H) ), 3.84-4.07 (m, 2 H), 4.65 (s, 1 H), 7.20-7.27 (m, 2 H), 7.61-7.70 (m, 3 H), 7.90 (s, 1 H), 8.06 ( d, 1 H), 8.61 - 8.63 (m, 1 H), 8.73 (s, 2 H), 8.96 (s, 1 H), 10.3 (s, 1 H).

實施例85-225：N，N-二甲基-2-{[(2-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)胺基甲醯基]胺基}-4-(三氟甲基)苯磺醯胺 Example 85-225: N,N-Dimethyl-2-{[(2-{4-[2-(propylamino)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidine Aminomethylamino]amino}-4-(trifluoromethyl)benzenesulfonamide

TLC：Rf 0.79(乙酸乙酯)；1H-NMR(DMSO-d6)：δ 0.90(t，3 H)，1.51-1.65(m，2 H)，2.75(s，6 H)，3.15-3.24(m，2 H)，7.12-7.18(m，2 H)，7.41-7.50(m，3 H)，7.56-7.64(m，1 H)，7.77(t，1 H)，7.94(d，1 H)，8.60(s，1 H)，8.71(s，2 H)，8.98(s，1 H)，10.3(s，1 H)。 TLC: Rf 0.79 (ethyl acetate); 1 H-NMR (DMSO-d 6 ): δ 0.90 (t, 3 H), 1.51-1.65 (m, 2 H), 2.75 (s, 6 H), 3.15- 3.24 (m, 2 H), 7.12-7.18 (m, 2 H), 7.41-7.50 (m, 3 H), 7.56-7.64 (m, 1 H), 7.77 (t, 1 H), 7.94 (d, 1 H), 8.60 (s, 1 H), 8.71 (s, 2 H), 8.98 (s, 1 H), 10.3 (s, 1 H).

實施例85-226：1-[2-(甲基磺醯基)-5-(三氟甲基)苯基]-3-(2-{4-[2-(丙胺基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)脲 Example 85-226: 1-[2-(Methylsulfonyl)-5-(trifluoromethyl)phenyl]-3-(2-{4-[2-(propylamino)-1,3 -thiazol-5-yl]phenoxy}-5-pyrimidinyl)urea

TLC：Rf 0.23(己烷：乙酸乙酯=1：2)；1H-NMR(DMSO-d6)：δ 0.91(t，3 H)，1.51-1.63(m，2 H)，3.16-3.23(m，2 H)，3.38(s，3 H)，7.11-7.18(m，2 H)，7.41-7.48(m，3 H)，7.64(dd，1 H)，7.77(t，1 H)，8.07(d，1 H)，8.63(d，1 H)，8.73(s，2 H)，8.96(s，1 H)，10.3(s，1 H)。 TLC: Rf 0.23 (hexane: ethyl acetate = 1:2); 1 H-NMR (DMSO-d 6 ): δ 0.91 (t, 3 H), 1.51-1.63 (m, 2 H), 3.16-3.23 (m, 2 H), 3.38 (s, 3 H), 7.11-7.18 (m, 2 H), 7.41-7.48 (m, 3 H), 7.64 (dd, 1 H), 7.77 (t, 1 H) , 8.07 (d, 1 H), 8.63 (d, 1 H), 8.73 (s, 2 H), 8.96 (s, 1 H), 10.3 (s, 1 H).

藥理實驗例： Pharmacological experiment: 藥理實驗例1：TrkA酵素阻害活性之測定(體外試驗) Pharmacological Experiment 1: Determination of TrkA Enzyme Inhibitory Activity (In Vitro Test)

對於TrkA阻害活性之測定使用含有LanthaScreenTM激酶分析 試藥(Invitrogen公司製造；Fluorescein-Poly GT、LanthaScreenTM Tb-PY20及TR-FRET Dilution Buffer)、TrkA(Invitrogen公司製造)、ATP(Sigma-Aldrich公司製造)、激酶反應緩衝液(0.01%Brij35(Sigma-Aldrich公司製造)、10mM MgCl2(Sigma-Aldrich公司製造)、1mM EGTA(Sigma-Aldrich公司製造)之50mM HEPES緩衝液(Sigma-Aldrich公司製造)(pH7.5))及0.5M EDTA(pH8.0)(Invitrogen公司製造)，以下述之方法實施。 For TrkA encumber measuring the activity of containing LanthaScreen TM Kinase Assay reagent (manufactured by Invitrogen Corporation; Fluorescein-Poly GT, LanthaScreen TM Tb-PY20 and TR-FRET Dilution Buffer), TrkA (Invitrogen Corporation), ATP (Sigma-Aldrich Corporation Manufactured, kinetic reaction buffer (0.01% Brij35 (manufactured by Sigma-Aldrich), 10 mM MgCl 2 (manufactured by Sigma-Aldrich), 1 mM EGTA (manufactured by Sigma-Aldrich), 50 mM HEPES buffer (manufactured by Sigma-Aldrich Co., Ltd.) (pH 7.5)) and 0.5 M EDTA (pH 8.0) (manufactured by Invitrogen Co., Ltd.) were carried out in the following manner.

將本發明化合物以二甲亞碸(以下，簡稱為DMSO)溶解，調製10mM溶液。於96洞盤中分注10mM之被驗化合物後以DMSO階段稀釋，調製3倍公比之稀釋系列。將該稀釋系列(DMSO溶液)以激酶反應緩衝液稀釋20倍，調製5倍濃度之本發明化合物溶液(DMSO濃度5%)。TrkA以激酶反應緩衝液稀釋，調製38.5ng/mL之溶液(酵素溶液)。三磷酸腺苷(以下，簡稱為ATP)預先以蒸餾水稀釋，調製10mM溶液後分注，於-20℃保存。將10mM ATP溶液及Fluorescein-Poly GT以激酶反應緩衝液稀釋，調製含有375mM ATP及500nM Fluorescein-Poly GT之溶液(ATP-基質溶液)。將0.5M EDTA(pH8.0)及LanthaScreenTM Tb-PY20以TR-FRET稀釋緩衝液稀釋，調製含有20mM EDTA及4nM LanthaScreenTM Tb-PY20之溶液(檢測用緩衝液)。 The compound of the present invention was dissolved in dimethyl sulfoxide (hereinafter abbreviated as DMSO) to prepare a 10 mM solution. A 10 mM test compound was dispensed into a 96-well plate and diluted in a DMSO phase to prepare a dilution series of 3 times the ratio. The diluted series (DMSO solution) was diluted 20-fold in a kinase reaction buffer to prepare a 5-fold concentration of the compound solution of the present invention (DMSO concentration 5%). TrkA was diluted in a kinase reaction buffer to prepare a 38.5 ng/mL solution (enzyme solution). Adenosine triphosphate (hereinafter abbreviated as ATP) was diluted with distilled water in advance, and a 10 mM solution was prepared, and then dispensed and stored at -20 °C. A 10 mM ATP solution and Fluorescein-Poly GT were diluted in a kinase reaction buffer to prepare a solution (ATP-matrix solution) containing 375 mM ATP and 500 nM Fluorescein-Poly GT. The 0.5M EDTA (pH8.0) and LanthaScreen TM Tb-PY20 diluted in TR-FRET dilution buffer, containing 20mM EDTA and modulation 4nM LanthaScreen TM Tb-PY20 solution of (detection buffer).

於96半洞分析盤中添加本發明化合物溶液(5μL/洞)及酵素溶液(10μL/洞)，將該盤於室溫使用盤攪拌機(IKATM MTS2/4計數微盤、IKA日本股份有限公司製造)攪拌10分鐘。於對照組及空白組添加含有5%DMSO之激酶反應緩衝液(5μL/洞)替代本發明化合物溶液。又，於空白組添加激酶反應緩衝液 (10μL/洞)替代酵素溶液後，於盤中添加ATP-基質溶液(10μL/洞)，開始激酶反應，將該盤於遮光下，於室溫使用盤攪拌機攪拌1小時(TrkA最終濃度：15.4ng/mL、基質最終濃度：200nM及ATP最終濃度：150μM)。於盤中添加檢測用緩衝液(25μL/洞)，將激酶反應停止，將該盤於遮光下，於室溫使用盤攪拌機攪拌30分鐘。使用Analyst GT(Molecular Devices日本股份有限公司製造)，於各洞照射340nm之激發光，測定520nm及495nm之螢光強度。將各洞之520nm之螢光強度除以495nm之螢光強度，算出時間分解螢光共鳴能量轉移(TR-FRET)比。 Add the compound solution of the present invention (5 μL/well) and the enzyme solution (10 μL/well) to the 96-half-hole analysis plate, and use the plate stirrer at room temperature (IKA TM MTS2/4 counting microdisk, IKA Japan Co., Ltd. Manufacture) Stir for 10 minutes. A kinase reaction buffer (5 μL/well) containing 5% DMSO was added to the control group and the blank group instead of the compound solution of the present invention. In addition, after adding the kinase reaction buffer (10 μL/well) to the blank group, the ATP-matrix solution (10 μL/well) was added to the plate to start the kinase reaction. The plate was shielded from light and used at room temperature. The mixer was stirred for 1 hour (TrkA final concentration: 15.4 ng/mL, final matrix concentration: 200 nM and ATP final concentration: 150 μM). A buffer for detection (25 μL/well) was added to the disk to stop the kinase reaction, and the plate was shaken under a light-shield for 30 minutes at room temperature using a pan mixer. The excitation light at 340 nm was irradiated to each well using Analyst GT (manufactured by Molecular Devices Japan Co., Ltd.), and the fluorescence intensity at 520 nm and 495 nm was measured. The time-resolved fluorescence resonance energy transfer (TR-FRET) ratio was calculated by dividing the 520 nm fluorescence intensity of each hole by the 495 nm fluorescence intensity.

本發明化合物之阻害率(%)使用以下之數式1算出。 The inhibition rate (%) of the compound of the present invention was calculated using the following formula 1.

[數1]阻害率(%)={1-(A X -A B )/(A C -A B )}×100 [Number 1] Damage rate (%) = {1 - (A X - A B ) / (A C - A B )} × 100

AX：添加本發明化合物時之TR-FRET比 A X : TR-FRET ratio when adding the compound of the present invention

AB：空白組之TR-FRET比 A B : TR-FRET ratio of blank group

AC：對照組之TR-FRET比 A C : TR-FRET ratio of the control group

本發明化合物50%阻害率之值(IC50值)根據本發明化合物各濃度中之阻害率而，從阻害曲線算出。 The value of the 50% inhibition rate of the compound of the present invention (IC 50 value) was calculated from the inhibition curve according to the resistance rate in each concentration of the compound of the present invention.

該結果為本發明化合物之IC50值在0.5μM以下，可知本發明化合物具有TrkA酵素阻害活性。例如數個本發明化合物之IC50值為如下述表1所示。 As a result, the IC 50 value of the compound of the present invention was 0.5 μM or less, and it was found that the compound of the present invention has TrkA enzyme inhibitory activity. For example, the IC 50 values of several of the compounds of the invention are shown in Table 1 below.

藥理實驗例2：對於Trk以外之其他激酶之酵素阻害活性試驗(選擇性實驗) Pharmacological Experiment 2: Enzyme inhibition activity test for other kinases other than Trk (selective experiment)

將被驗物質(本發明化合物及比較化合物)溶解於二甲亞碸，另以二甲亞碸稀釋，調整3μm試驗濃度100倍濃度之溶液。該溶液另以分析緩衝液(20mM HEPES、0.01%TritonX-100、2mM DTT，pH7.5)稀釋25倍，作為被驗物質溶液。陽性對照物質亦同樣操作 而，調整為陽性對照物質溶液。 The test substance (the compound of the present invention and the comparative compound) was dissolved in dimethyl hydrazine, and diluted with dimethyl sulfoxide, and a solution having a concentration of 100 μm at a test concentration of 3 μm was adjusted. This solution was further diluted 25 times with an assay buffer (20 mM HEPES, 0.01% Triton X-100, 2 mM DTT, pH 7.5) to prepare a test substance solution. Positive control substances are also operated However, it was adjusted to a positive control substance solution.

將以分析緩衝液調整之5μL之4倍濃度被驗物質溶液、5μL之4倍濃度基質/ATP/金屬溶液(鎂)及10μL之2倍濃度激酶溶液於聚丙烯製造之384洞盤之洞內混合，於室溫進行反應1小時。添加60μL之終止緩衝液(termination buffer)(QuickScout Screening Assist MSA；Carna Biosciences)將反應停止。將反應溶液中之基質肽與磷酸化肽分離、定量。激酶反應以從基質肽高峰高度(S)與磷酸化肽高峰高度(P)計算之生成物比(P/(P+S))評估。作為其他之激酶使用例如Abl、c-Met、b-Raf、c-Kit及KDR之激酶，進行激酶選擇性實驗。以下之表2表示於各別激酶酵素阻害活性試驗中使用之基質、基質濃度、ATP濃度及陽性對照物質。 4 times the concentration of 5 μL of the assay solution, 5 μL of the matrix/ATP/metal solution (magnesium) and 10 μL of the 2x concentration of the kinase solution in a 384-well dish made of polypropylene. The mixture was mixed and allowed to react at room temperature for 1 hour. The reaction was stopped by the addition of 60 μL of a termination buffer (QuickScout Screening Assist MSA; Carna Biosciences). The matrix peptide in the reaction solution is separated and quantified from the phosphorylated peptide. The kinase reaction was evaluated as the product ratio (P/(P+S)) calculated from the peak height (S) of the matrix peptide and the peak height (P) of the phosphorylated peptide. Kinase selectivity experiments were performed as kinases for other kinases such as Abl, c-Met, b-Raf, c-Kit and KDR. Table 2 below shows the matrix, matrix concentration, ATP concentration and positive control substance used in the respective kinase enzyme inhibitory activity tests.

將含有所有反應組成之對照洞之平均信號作為0%阻害、背景洞(未添加酵素)之平均信號作為100%阻害，從各被驗物質試驗洞之平均信號計算阻害率。其結果，對於在3μM濃度之本發明化合物，各激酶之阻害率為如以下表3所示。 The average signal of the control wells containing all the reaction components was taken as the 100% inhibition of the average signal of 0% inhibition and background hole (without added enzyme), and the damage rate was calculated from the average signal of each test substance test hole. As a result, the resistance of each kinase to the compound of the present invention at a concentration of 3 μM was as shown in Table 3 below.

從該結果可知本發明化合物對於TrkA以外之其他激酶，例如Abl、c-Met、b-Raf、c-Kit及KDR之激酶之阻害弱，對於TrkA有強的阻害。換言之，本發明化合物從藥理實施例1之結果來看，對於TrkA阻害，IC50在0.5μM以下，為非常強力，另一方面，從藥理實施例2之結果來看，對於TrkA以外之上述激酶，即使於3μM濃度之化合物，只阻害0%至約30%。所以可知，本發明化合物對於TrkA阻害之選擇性高，具有優越之激酶選擇性。 From the results, it is understood that the compounds of the present invention are weakly resistant to kinases other than TrkA, such as Abl, c-Met, b-Raf, c-Kit and KDR, and have strong resistance to TrkA. In other words, from the results of Pharmacological Example 1, the compound of the present invention has an IC 50 of 0.5 μM or less for TrkA inhibition, and is very strong. On the other hand, from the results of Pharmacological Example 2, the above kinase other than TrkA Even at a concentration of 3 μM, only 0% to about 30% are blocked. Therefore, it is understood that the compound of the present invention has high selectivity for TrkA inhibition and superior kinase selectivity.

藥理實驗例3：測定使用人類TrkA表現細胞之TrkA激酶阻害活性 Pharmacological Experiment Example 3: Determination of TrkA kinase inhibitory activity using human TrkA expressing cells

對於細胞系之TrkA激酶之阻害活性使用人類TrkA及表現NFAT-bla之CHO-K1細胞(CellSenserTM TrkA-NFAT-bla CHO-K1細胞，Invitrogen公司製造)實施。 For cell lines TrkA kinase activity encumber the use of human TrkA and NFAT-bla expression of CHO-K1 cells (CellSenser TM TrkA-NFAT-bla CHO-K1 cells, Invitrogen Corporation) embodiment.

於分析前一天將CellSenserTM TrkA-NFAT-bla CHO-K1細胞懸濁於含有分析培養基(0.5%透析處理之牛胎兒血清(Invitrogen公司製造)、0.1mM非必需胺基酸(Invitrogen公司製造)、1mM丙酮酸鈉(Invitrogen公司製造)及抗生物質(100U/mL盤尼西林(penicillin)及100μg/mL鏈黴素(streptomycin)(Invitrogen公司製造)) 之Opti-MEM1 Reduced Serum Medium(Invitrogen公司製造))中，以2.4×104細胞/40μL/洞之密度播種於96洞透明底盤(Corning公司製造，產品編號：3882)。又，於一部分洞只添加40μL/洞之分析培養基(無細胞)。於分析當天於96洞盤(Costar公司製造，產品編號：3363)中分注10mM之本發明化合物(DMSO溶液)後以DMSO階段稀釋，調製3倍公比之稀釋系列。將該稀釋系列以分析培養基稀釋100倍，調製10倍濃度之本發明化合物溶液(DMSO濃度1%)。於播種細胞之盤中添加本發明化合物5μL/洞，於5%CO2、95%空氣、37℃之CO2恆溫箱內保溫30分鐘。對照組及空白組使用含有1%DMSO之分析培養基替代本發明化合物溶液添加5μL/洞。之後於盤中添加含有NGF(老鼠2.5s、天然型、Invitrogen公司製造)之分析培養基5μL/洞(NGF之最終濃度：50ng/mL)，於5%CO2、95%空氣、37℃之CO2恆溫箱內保溫5小時。空白群添加5μL/洞之分析培養基替代NGF。於盤中添加報導分析(reporter assay)檢測用試藥10μL/洞後，於遮光下，於室溫保溫120分鐘。又，報導分析檢測用試藥以LiveBLAzerTM-FRET B/G Loading Kit(Invitrogen公司製造)調製。使用Analyst GT((Molecular Devices日本股份有限公司製造)，於各洞掃射405nm之激發光，測定460nm及530nm之螢光強度。使用下述之數式2算出各洞之時間分解螢光共鳴能轉移(TR-FRET)比。 Analysis one day before the CellSenser TM TrkA-NFAT-bla CHO -K1 cells are suspended in assay medium comprising (0.5% of dialyzed bovine fetal serum (manufactured by Invitrogen), 0.1 mM non-essential amino acids (Invitrogen Corporation), 1 mM sodium pyruvate (manufactured by Invitrogen) and anti-biomass (100 U/mL penicillin and 100 μg/mL streptomycin (manufactured by Invitrogen)) in Opti-MEM1 Reduced Serum Medium (Invitrogen) Seeded at a density of 2.4 × 10 4 cells / 40 μL / hole in a 96-hole transparent chassis (manufactured by Corning, product number: 3882). In addition, only 40 μL/well of assay medium (no cells) was added to a portion of the well. On the day of analysis, 10 mM of the compound of the present invention (DMSO solution) was dispensed into a 96-well plate (manufactured by Costar, product number: 3363), and then diluted in a DMSO stage to prepare a dilution series of 3 times the ratio. The diluted series was diluted 100-fold with an analysis medium to prepare a 10-fold concentration of the compound solution of the present invention (DMSO concentration: 1%). 5 μL/well of the compound of the present invention was added to the disk of the seeded cells, and the cells were incubated in a CO 2 incubator at 5% CO 2 , 95% air, and 37 ° C for 30 minutes. The control group and the blank group were added with 5 μL/well using an assay medium containing 1% DMSO instead of the compound solution of the present invention. Then, an assay medium containing NGF (rat 2.5 s, natural type, manufactured by Invitrogen) was added to the plate at 5 μL/well (final concentration of NGF: 50 ng/mL), and CO at 5% CO 2 , 95% air, and 37 ° C. 2 Keep the incubator for 5 hours. The blank group was supplemented with 5 μL/well of assay medium instead of NGF. After adding 10 μL/well of the test reagent for the reporter assay to the plate, the sample was incubated at room temperature for 120 minutes under light-shielding. Further, the detection reagent analysis reported in LiveBLAzer TM -FRET B / G Loading Kit (Invitrogen Corporation) modulation. The excitation intensity at 460 nm and 530 nm was measured by using Analyst GT (manufactured by Molecular Devices Japan Co., Ltd.) in each hole, and the fluorescence intensity at 460 nm and 530 nm was measured. The time-resolved fluorescence resonance energy transfer of each hole was calculated using the following formula 2. (TR-FRET) ratio.

[數2]TR-FRET比=(A 460x -A 460F )/(A 530X -A 530F ) [Number 2] TR-FRET ratio = (A 460x - A 460F ) / (A 530X - A 530F )

A460X：本發明化合物、對照組或空白組460nm之螢光強度 A 460X : Fluorescence intensity of 460 nm of the compound of the present invention, control group or blank group

A460F：無細胞460nm之螢光強度 A 460F : Fluorescence intensity without cell 460nm

A530X：本發明化合物、對照組或空白組530nm之螢光強度 A 530X : Fluorescence intensity of 530 nm of the compound of the present invention, control group or blank group

A530F：無細胞530nm之螢光強度 A 530F : Fluorescence intensity of cell-free 530nm

本發明化合物之TR-FRET阻害率(%)使用下述之數3算出。 The TR-FRET inhibition rate (%) of the compound of the present invention was calculated using the following number 3.

[數3]阻害率(%)={1-(A X -A B )/(A C -A B )}×100 [Number 3] Damage rate (%) = {1 - (A X - A B ) / (A C - A B )} × 100

AX：添加本發明化合物時之TR-FRET比 A X : TR-FRET ratio when adding the compound of the present invention

AB：空白組之TR-FRET比 A B : TR-FRET ratio of blank group

AC：對照組之TR-FRET比 A C : TR-FRET ratio of the control group

本發明化合物之IC50值係根據於本發明化合物之各濃度之阻害率而，從阻害曲線算出。 The IC 50 value of the compound of the present invention is calculated from the inhibition curve based on the degree of inhibition of each concentration of the compound of the present invention.

該結果，本發明化合物之IC50值在0.5μM以下，可知本發明化合物具有TrkA阻害活性。例如數個本發明化合物之IC50值為如下述表4所示。 As a result, the compound of the present invention has an IC 50 value of 0.5 μM or less, and it is understood that the compound of the present invention has TrkA inhibitory activity. For example, the IC 50 values of several of the compounds of the invention are shown in Table 4 below.

藥理實驗例4：對於老鼠NGF引起血管透過性亢進之抑制作用(體內試驗) Pharmacological Experiment 4: Inhibition of vascular hyperpermeability induced by NGF in mice (in vivo test)

評估本發明化合物於體內對於TrkA之阻害活性。於剃掉背部毛的雄性CD(SD)IGS老鼠(7至9週齡、日本Charles River公司製造)經口投予溶解於介質之本發明化合物(投予容量：5mL/kg)。於對照群及正常群，經口投予介質(投予容量：5mL/kg)。投予6或12小 時後在氟烷麻醉下，於背部3個地方皮內投予使用含有0.1%BSA(Sigma-Aldrich公司製造)之生理食鹽液調製之3μg/mL之NGF(老鼠2.5s、天然型、Invitrogen公司製造)溶液(投予容量；50μL/site)。於正常群，於背部3個地方皮內投予含有0.1%BSA之生理食鹽液(投予容量；50μL/site)。皮內投予後馬上於尾靜脈內投予以生理食鹽液溶解之1%伊凡斯藍(Evans blue)(東京化成股份有限公司製造)(投予容量：3mL/kg)。投予10分後切斷腹部大動脈，放血致死。切取背部皮膚之皮內投予部位(3個地方)，將該皮膚試樣一個個移至48洞盤(旭硝子公司製造)之各洞中。於盤中每個洞加入甲醯胺0.8mL/洞，蓋上蓋子後於60℃保溫一晚。將200μL之甲醯胺萃取液移至96洞盤，使用吸光微量盤分析儀(Microplate reader)(SpectraMAX190，Molecular Devices日本股份有限公司製造)測定甲醯胺中萃取出之伊凡斯藍之吸光度(波長：620nm)。同時測定溶解於甲醯胺之伊凡斯藍之標品(0、0.78、1.56、3.13、6.25、12.5、25及50μg/mL)之吸光度(波長：620nm)作成校正曲線。從該校正曲線與各試樣之吸光度算出各試樣之伊凡斯藍濃度。算出從同一個體採取之3個地方之皮膚試樣之伊凡斯藍濃度之平均值，作為該個體之值。使用以下之數式4算出本發明化合物之老鼠NGF引起血管透過性亢進抑制率。 The compounds of the invention are evaluated for their inhibitory activity against TrkA in vivo. Male CD (SD) IGS mice (7 to 9 weeks old, manufactured by Charles River, Japan) shaved off the back hair were orally administered with a compound of the present invention dissolved in a medium (administration volume: 5 mL/kg). The medium was administered orally in the control group and the normal group (administration capacity: 5 mL/kg). Give 6 or 12 small Then, under the halothane anesthesia, 3 μg/mL of NGF (rat 2.5s, natural type, Invitrogen) prepared by using a physiological saline solution containing 0.1% BSA (manufactured by Sigma-Aldrich) was intradermally administered in three places on the back. Manufacture) solution (administration capacity; 50 μL/site). In the normal group, a physiological saline solution containing 0.1% BSA (administered volume; 50 μL/site) was intradermally administered in three places on the back. Immediately after intradermal administration, 1% Evans blue (manufactured by Tokyo Chemical Industry Co., Ltd.) in which physiological saline solution was dissolved was administered in the tail vein (administration capacity: 3 mL/kg). After giving 10 minutes, the abdominal aorta was cut off and blood was sacrificed. The intradermal administration site (three places) of the back skin was cut out, and the skin samples were individually transferred to each hole of a 48-hole disk (manufactured by Asahi Glass Co., Ltd.). Add 0.8 mL/well of methotrexate to each well of the plate, cover and heat at 60 ° C for one night. 200 μL of the methotrexate extract was transferred to a 96-well plate, and the absorbance of the Evans blue extracted from the formamide was measured using a Microplate reader (SpectraMAX 190, manufactured by Molecular Devices Japan Co., Ltd.). Wavelength: 620 nm). At the same time, the absorbance (wavelength: 620 nm) of the standards (0, 0.78, 1.56, 3.13, 6.25, 12.5, 25, and 50 μg/mL) of Evans blue dissolved in formamide was measured to prepare a calibration curve. The Evans blue concentration of each sample was calculated from the calibration curve and the absorbance of each sample. The average value of the Evans blue concentration of the skin samples from three places taken from the same individual was calculated as the value of the individual. The rat NGF of the compound of the present invention was used to calculate the rate of inhibition of vascular permeability by the following formula 4.

[數4]抑制率(%)={1-(A X -A N )/(A C -A N )}×100 [Number 4] Inhibition rate (%) = {1 - (A X - A N ) / (A C - A N )} × 100

AX：被驗化合物之伊凡斯藍濃度(同一個體之3試樣之平均值) A X : Evans blue concentration of the test compound (average of 3 samples of the same individual)

AN：正常群之伊凡斯藍濃度(同一個體之3試樣之平均值) A N : Evans blue concentration of the normal group (average of 3 samples of the same individual)

AC：對照群之伊凡斯藍濃度(同一個體之3試樣之平均值) A C : Evans blue concentration of the control group (average of 3 samples of the same individual)

其結果，本發明化合物(3mg/kg；投予6小時後)之老鼠NGF引起血管透過性亢進抑制率為約70%。 As a result, the NGF of the compound of the present invention (3 mg/kg; after administration for 6 hours) caused an vascular hyperosmotic inhibition rate of about 70%.

例如數個本發明化合物(1mg/kg；投予12小時後)之老鼠NGF引起血管透過性亢進抑制率為如以下表5所示，可知本發明化合物係根據Trk阻害活性，而為體內活性強之化合物，為具有持續性活性之化合物。 For example, in a plurality of compounds of the present invention (1 mg/kg; after administration for 12 hours), the NGF-induced vascular permeability inhibition rate is as shown in Table 5 below, and it is understood that the compound of the present invention is active in vivo according to Trk inhibitory activity. The compound is a compound having sustained activity.

另一方面，於專利文獻3記載之實施例42之老鼠NGF引起血管透過性亢進抑制率為21%(1mg/kg；投予12小時後)，對於根據Trk阻害活性之體內活性，為非常弱的化合物。 On the other hand, the NGF of the mouse of Example 42 described in Patent Document 3 caused an vascular hyperinhibition inhibition rate of 21% (1 mg/kg; after administration for 12 hours), and was very weak against the in vivo activity against Trk inhibitory activity. compound of.

[製劑例] [Formulation Example] 製劑例1 Formulation Example 1

將以下之各成分根據常法混合後打錠，獲得每錠中含有10mg活性成分之錠劑1萬錠。 Each of the following components was mixed according to a usual method and then tableted to obtain 10,000 tablets of a tablet containing 10 mg of the active ingredient per tablet.

．1-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-苯基-5-(三氟甲基)-3-吡啶基]脲…100g . 1-(2-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-[2 -Phenyl-5-(trifluoromethyl)-3-pyridyl]urea...100g

．羧甲基纖維素鈣(崩解劑)…20g . Carboxymethylcellulose calcium (disintegrant)...20g

．硬脂酸鎂(潤滑劑)…10g . Magnesium stearate (lubricant)...10g

．微結晶纖維素…870g . Microcrystalline cellulose...870g

製劑例2 Formulation Example 2

將以下之各成分根據常法混合後以除塵過濾器過濾，每支安瓿填充5mL，以微波加熱滅菌，獲得每安瓿中含有20mg活性成分之安瓿1萬支。 The following components were mixed according to the usual method and filtered with a dust filter. Each ampule was filled with 5 mL, and sterilized by microwave heating to obtain 10,000 ampoules containing 20 mg of the active ingredient per ampule.

．1-(2-{4-[2-(2-側氧基-1-吡咯啶基)-1，3-噻唑-5-基]苯氧基}-5-嘧啶基)-3-[2-苯基-5-(三氟甲基)-3-吡啶基]脲..200g . 1-(2-{4-[2-(2-Sideoxy-1-pyrrolidinyl)-1,3-thiazol-5-yl]phenoxy}-5-pyrimidinyl)-3-[2 -Phenyl-5-(trifluoromethyl)-3-pyridyl]urea..200g

．甘露糖醇…20g . Mannitol...20g

．蒸餾水…50L . Distilled water...50L

(產業上之可利用性) (industrial availability)

本發明之化合物具有Trk阻害活性，對於關於Trk之疾病，例如疼痛、搔癢症、下部尿路障害、氣喘、過敏性鼻炎、發炎性腸疾病或查加斯病等疾病之預防及/或治療有效。 The compound of the present invention has Trk inhibitory activity and is effective for prevention and/or treatment of diseases related to Trk such as pain, pruritus, lower urinary tract disorders, asthma, allergic rhinitis, inflammatory bowel disease or Chagas disease. .

Claims (17)

一種通式(I)表示之化合物、其鹽、其N-氧化物、其溶劑化物或該等之前驅藥； 式中，環Cy1表示C3至10之單環式碳環或二環式碳環、或4至10員單環式雜環或二環式雜環、R1表示(1)鹵素原子、(2)可經鹵素原子或側氧基取代之C1至6烷基、(3)可經鹵素原子或C1至3烷基取代之C3至6環烷基、(4)可經鹵素原子或側氧基取代之C1至6烷基之碳原子以氧原子置換後之基、或(5)可經鹵素原子或C1至3烷基取代之C3至6環烷基之碳原子以氧原子置換後之基；R2表示(1)可經選自由下列者所成群組之取代基取代之C1至6烷基、C2至6烯基或C2至6炔基：(i)鹵素原子、(ii)羥基、(iii)-NH(C1至3烷基)、(iv)-N(C1至3烷基)2、 (v)胺基、(vi)氰基、(vii)硝基、(viii)C1至4烷基磺醯基、(ix)磺醯胺基、(x)C1至4烷基磺醯胺基、(xi)側氧基、(xii)羧基、(xiii)-C(O)(O-C1至4烷基)、(xiv)膦醯基氧基、(xv)-OP(O)(O-C1至4烷基)2、(xvi)胺基甲醯基、(xvii)C1至4烷基醯胺基、及(xviii)C1至4烷基胺基甲酸酯基、(2)氫原子、(3)羥基、(4)羧基、(5)-C(O)(O-C1至4烷基)、(6)膦醯基氧基、(7)-OP(O)(O-C1至4烷基)2、(8)胺基、(9)氰基、(10)硝基、(11)C1至4烷基磺醯基、 (12)磺醯胺基、(13)C1至4烷基磺醯胺基、(14)側氧基、(15)胺基甲醯基、(16)C1至4烷基醯胺基、(17)C1至4烷基胺基甲酸酯基或(18)式中，箭頭a表示與環Cy1結合，X表示鍵結、氧原子、C=O或NH，環Cy2表示C3至10之單環式碳環或二環式碳環、或4至10員單環式雜環或二環式雜環；R6表示(1)可經選自由下列者所成群組之取代基取代之C1至6烷基、C2至6烯基、C2至6炔基或C3至6環烷基：(i)鹵素原子、(ii)羥基、(iii)側氧基、(iv)-NH(C1至3烷基)、(v)-N(C1至3烷基)2、(vi)C1至6烷氧基、(vii)胺基、(viii)氰基、 (ix)硝基、(x)C1至4烷基磺醯基、(xi)磺醯胺基、(xii)C1至4烷基磺醯胺基、(xiii)羧基、(xiv)-C(O)(O-C1至4烷基)、(xv)膦醯基氧基、(xvi)-OP(O)(O-C1至4烷基)2、(xvii)胺基甲醯基、(xviii)C1至4烷基醯胺基、及(xix)C1至4烷基胺基甲酸酯基、(2)鹵素原子、(3)C1至4烷氧基、(4)膦醯基氧基、(5)-OP(O)(O-C1至4烷基)2、(6)磺醯胺基、(7)側氧基、(8)-NH(C1至3烷基)、(9)-N(C1至3烷基)2、(10)羧基、(11)-C(O)(O-C1至4烷基)、(12)胺基甲醯基、(13)C1至4烷基醯胺基、(14)羥基、 (15)胺基、(16)氰基、(17)硝基、(18)C1至4烷基磺醯基、(19)C1至4烷基磺醯胺基、或(20)C1至4烷基胺基甲酸酯基；A1及A2各自獨立地表示=CR3-、=CH-或=N-；A3、A4、A5及A6各自獨立地表示=CR4-或=N-；R3表示(1)鹵素原子、或是(2)可經鹵素原子取代之C1至3烷基或C1至3烷氧基；R4表示(1)鹵素原子、(2)可經鹵素原子取代之C1至3烷基或C1至3烷氧基、或是(3)氫原子；Y表示氧原子、可經氧化之硫原子、亞甲基或C=O；Z表示形成 或 之環之碳原子以氧原子置換後之基；式中，R5表示鹵素原子、羥基或可經羥基取代之C1至4烷基；R7各自獨立地為(1)可經選自由下列者所成群組之取代基取代之C1至6烷基、C3至6環烷基、C1至6烷基之碳原子以氧原子置換後之基、或C3至6環烷基之碳原子以氧原子置換後之基：(i)鹵素原子、(ii)C3至6環烷基、(iii)羥基、(iv)側氧基、及(v)4至6員單環式雜環、或是(2)氫原子；箭頭b、c、d及e表示與噻唑環結合、p表示0至5之整數、q表示0至7之整數、r表示0至2之整數、w表示1至5之整數、u表示0至2之整數，惟p、q、r及u各別表示2以上之整數時，R1、R3、R5及R6各自獨立，可相同亦可不同。 a compound represented by the formula (I), a salt thereof, an N-oxide thereof, a solvate thereof or the like; Wherein the ring Cy 1 represents a C 3 to 10 monocyclic carbocyclic ring or a bicyclic carbocyclic ring, or a 4 to 10 membered monocyclic heterocyclic ring or a bicyclic heterocyclic ring, and R 1 represents (1) a halogen atom, ( 2) a C1 to 6 alkyl group which may be substituted by a halogen atom or a pendant oxy group, (3) a C3 to 6 cycloalkyl group which may be substituted by a halogen atom or a C1 to 3 alkyl group, (4) may pass through a halogen atom or a side oxygen a group in which a carbon atom of a C1 to 6 alkyl group is substituted with an oxygen atom, or (5) a carbon atom of a C3 to 6 cycloalkyl group which may be substituted by a halogen atom or a C1 to 3 alkyl group is substituted with an oxygen atom And R 2 represents (1) a C1 to 6 alkyl group, a C2 to 6 alkenyl group or a C2 to 6 alkynyl group which may be substituted with a substituent selected from the group consisting of: (i) a halogen atom, (ii) Hydroxy, (iii)-NH(C1 to 3 alkyl), (iv)-N(C1 to 3 alkyl) 2 , (v) amine, (vi) cyano, (vii) nitro, (viii) C1 to 4 alkylsulfonyl, (ix) sulfonylamino, (x) C1 to 4 alkylsulfonylamino, (xi) pendant oxy, (xii) carboxy, (xiii)-C(O) (O-C1 to 4 alkyl), (xiv) phosphinyloxy, (xv)-OP(O)(O-C1 to 4 alkyl) 2 , (xvi)aminomethylcarbenyl, (xvii) C1 to 4 alkyl amidino group, and (xviii) C1 to 4 alkyl urethane group, (2) hydrogenogen , (3) hydroxyl, (4) carboxyl, (5)-C(O) (O-C1 to 4 alkyl), (6) phosphinyloxy, (7)-OP(O) (O-C1 To 4 alkyl) 2 , (8) amine, (9) cyano, (10) nitro, (11) C1 to 4 alkyl sulfonyl, (12) sulfonylamino, (13) C1 to 4 alkylsulfonylamino, (14) pendant oxy, (15) aminomethyl decyl, (16) C1 to 4 alkyl guanylamino, (17) C1 to 4 alkyl urethane Or (18) Wherein the arrow a represents a bond with the ring Cy 1 , X represents a bond, an oxygen atom, C=O or NH, and the ring Cy 2 represents a C 3 to 10 monocyclic carbocyclic ring or a bicyclic carbocyclic ring, or 4 to 10 a monocyclic heterocyclic ring or a bicyclic heterocyclic ring; R 6 represents (1) a C1 to 6 alkyl group, a C2 to 6 alkenyl group, a C2 to 6 alkyne which may be substituted with a substituent selected from the group consisting of Or a C3 to 6 cycloalkyl group: (i) a halogen atom, (ii) a hydroxyl group, (iii) a pendant oxy group, (iv) -NH(C1 to 3 alkyl), (v)-N (C1 to 3 alkane) 2 ), (vi) C1 to 6 alkoxy, (vii) amine, (viii) cyano, (ix) nitro, (x) C1 to 4 alkyl sulfonyl, (xi) sulfonamide (xii) C1 to 4 alkylsulfonylamino, (xiii) carboxyl, (xiv)-C(O)(O-C1 to 4 alkyl), (xv)phosphinyloxy, (xvi) -OP(O)(O-C1 to 4 alkyl) 2 , (xvii) aminomethyl decyl, (xviii) C1 to 4 alkyl guanylamino, and (xix) C1 to 4 alkyl carbamic acid Ester group, (2) halogen atom, (3) C1 to 4 alkoxy group, (4) phosphinyloxy group, (5)-OP (O) (O-C1 to 4 alkyl group) 2 , (6) Sulfonamide, (7) pendant oxy, (8)-NH (C1 to 3 alkyl), (9)-N (C1 to 3 alkyl) 2 , (10) carboxyl, (11)-C ( O) (O-C1 to 4 alkyl), (12) aminomethyl decyl, (13) C1 to 4 Alkylamino, (14) hydroxy, (15) amine, (16) cyano, (17) nitro, (18) C1 to 4 alkyl sulfonyl, (19) C1 to 4 alkyl sulfonium Amino, or (20) C1 to 4 alkyl urethane groups; A 1 and A 2 each independently represent =CR 3 -, =CH- or =N-; A 3 , A 4 , A 5 and A 6 each independently represents =CR 4 - or =N-; R 3 represents (1) a halogen atom, or (2) a C1 to 3 alkyl group or a C1 to 3 alkoxy group which may be substituted by a halogen atom; R 4 And (2) a halogen atom, (2) a C1 to 3 alkyl group or a C1 to 3 alkoxy group which may be substituted by a halogen atom, or (3) a hydrogen atom; Y represents an oxygen atom, an oxidizable sulfur atom, or a sub Methyl or C=O; Z means formation or Wherein the carbon atom of the ring is substituted with an oxygen atom; wherein R 5 represents a halogen atom, a hydroxyl group or a C1 to 4 alkyl group which may be substituted by a hydroxyl group; and R 7 is independently independently (1) may be selected from the group consisting of a group of substituents substituted with a C1 to 6 alkyl group, a C3 to 6 cycloalkyl group, a C1 to 6 alkyl group having a carbon atom substituted with an oxygen atom, or a C3 to 6 cycloalkyl group having an oxygen atom The base after atomic substitution: (i) a halogen atom, (ii) a C3 to 6 cycloalkyl group, (iii) a hydroxyl group, (iv) a pendant oxy group, and (v) a 4 to 6 membered monocyclic heterocyclic ring, or (2) a hydrogen atom; arrows b, c, d, and e represent a bond with a thiazole ring, p represents an integer of 0 to 5, q represents an integer of 0 to 7, r represents an integer of 0 to 2, and w represents 1 to 5 An integer and u represent an integer of 0 to 2, and when p, q, r, and u each represent an integer of 2 or more, R 1 , R 3 , R 5 , and R 6 are each independently and may be the same or different. 如申請專利範圍第1項所述之化合物，其中，通式(I)為 式中，所有符號與申請專利範圍第1項所述之符號同意義。 The compound of claim 1, wherein the formula (I) is In the formula, all symbols have the same meaning as the symbols described in item 1 of the patent application. 如申請專利範圍第2項所述之化合物，其中，通式(I-1)為 式中，所有符號與申請專利範圍第1項所述之符號同意義。 A compound according to claim 2, wherein the formula (I-1) is In the formula, all symbols have the same meaning as the symbols described in item 1 of the patent application. 如申請專利第2項或第3項所述之化合物，其中，環Cy1為苯環或5至6員單環式芳族雜環。 The compound of claim 2, wherein the ring Cy 1 is a benzene ring or a 5 to 6 membered monocyclic aromatic heterocyclic ring. 如申請專利範圍第1項至第4項中任何一項所述之化合物，其中，A1及A2任何一方為=N-且另一方為=CH-，或是雙方均為=N-，A3、A4、A5及A6為=CH-。 The compound of any one of claims 1 to 4, wherein either one of A 1 and A 2 is =N- and the other is =CH-, or both are =N-, A 3 , A 4 , A 5 and A 6 are =CH-. 如申請專利範圍第1項所述之化合物，其中，通式(I)為 或 式中，pa表示0至4之整數，pb表示0至3之整數，其他之符號與如申請專利範圍第1項所述之符號同意義，惟pa及pb各別為2以上之整數時，R1可相同亦可不同。 The compound of claim 1, wherein the formula (I) is or Wherein, pa represents an integer from 0 to 4, pb represents an integer from 0 to 3, and the other symbols have the same meaning as the symbols described in the first item of the patent application, but if pa and pb are each an integer of 2 or more, R 1 may be the same or different. 如申請專利範圍第6項所述之化合物，其中，A1及A2任何一方為=N-且另一方為=CH-，或是雙方均為=N-，A3、A4、A5及A6為=CH-。 The compound according to claim 6, wherein either one of A 1 and A 2 is =N- and the other is =CH-, or both are =N-, A 3 , A 4 , A 5 And A 6 is =CH-. 如申請專利範圍第1項所述之化合物，其中，通式(I)為 式中，所有符號與如申請專利範圍第1項及第6項所述之符號同意義。 The compound of claim 1, wherein the formula (I) is Wherein, all symbols have the same meaning as the symbols described in items 1 and 6 of the scope of the patent application. 如申請專利範圍第8項所述之化合物，其中，A1及A2任何一 方為=N-且另一方為=CH-，或是雙方均為=N-，A3、A4、A5及A6為=CH-。 The compound of claim 8, wherein either one of A 1 and A 2 is =N- and the other is =CH-, or both are =N-, A 3 , A 4 , A 5 And A 6 is =CH-. 一種醫藥組成物，係含有如申請專利範圍第1項所述之通式(I)表示之化合物、其鹽、其N-氧化物、其溶劑化物或該等之前驅藥作為有效成分。 A pharmaceutical composition comprising a compound represented by the formula (I), a salt thereof, an N-oxide thereof, a solvate thereof or the prodrug of the above-mentioned patent application, as an active ingredient. 如申請專利範圍第10項所述之醫藥組成物，其為Trk阻害劑。 The pharmaceutical composition according to claim 10, which is a Trk inhibitor. 如申請專利範圍第10項所述之醫藥組成物，其為疼痛、搔癢症、下部尿路障害、氣喘、過敏性鼻炎、發炎性腸疾病或查加斯病之預防及/或治療劑。 The pharmaceutical composition according to claim 10, which is a preventive and/or therapeutic agent for pain, pruritus, lower urinary tract dysfunction, asthma, allergic rhinitis, inflammatory bowel disease or Chagas disease. 如申請專利範圍第12項所述之醫藥組成物，其中，疼痛為變形性關節炎伴隨之疼痛、癌性疼痛、慢性腰痛症、骨質疏鬆症伴隨之腰痛、骨折痛、風濕性關節炎伴隨之疼痛、神經障害性疼痛、帶狀疱疹後疼痛、糖尿病性神經障害伴隨之疼痛、纖維肌痛症、胰臟炎伴隨之疼痛、間質性膀胱炎伴隨之疼痛、子宮內膜症伴隨之疼痛、過敏性腸症候群伴隨之疼痛、偏頭痛或齒髓炎伴隨之疼痛者。 The pharmaceutical composition according to claim 12, wherein the pain is accompanied by pain associated with osteoarthritis, cancer pain, chronic low back pain, low back pain accompanying osteoporosis, fracture pain, and rheumatoid arthritis. Pain, neuropathic pain, post-herpetic pain, pain associated with diabetic neurological disorders, fibromyalgia, pain associated with pancreatitis, pain associated with interstitial cystitis, pain associated with endometriosis, Pain associated with pain, migraine or orthodontic pain associated with irritable bowel syndrome. 一種醫藥，為由如申請專利範圍第1項所述之通式(I)表示之化合物、其鹽、其N-氧化物、其溶劑化物或該等之前驅藥，與選自對乙醯胺基酚(acetaminophen)、非類固醇性抗炎症藥、鴉片類藥、抗憂鬱藥、抗癲癇藥、N-甲基-D-天冬胺酸拮抗藥、肌肉鬆弛藥、抗心律不整藥、類固醇藥及雙磷酸鹽藥之至少一種以上組合所形成者。 A medicine, which is a compound represented by the formula (I), a salt thereof, an N-oxide thereof, a solvate thereof or the like, as described in the first paragraph of the patent application, and a phthalimide Acetaminophen, non-steroidal anti-inflammatory drugs, opioids, antidepressants, antiepileptics, N-methyl-D-aspartate antagonists, muscle relaxants, antiarrhythmics, steroids And at least one combination of bisphosphonates. 一種疼痛、搔癢症、下部尿路障害、氣喘、過敏性鼻炎、發炎性腸疾病或查加斯病之預防及/或治療方法，其係於病患投予 有效量之如申請專利範圍第1項所述之通式(I)表示之化合物、其鹽、其N-氧化物、其溶劑化物或該等之前驅藥。 A method for preventing and/or treating pain, pruritus, lower urinary tract disorders, asthma, allergic rhinitis, inflammatory bowel disease or Chagas disease, which is administered to a patient An effective amount is a compound represented by the formula (I), a salt thereof, an N-oxide thereof, a solvate thereof or a prodrug thereof as described in the first paragraph of the patent application. 一種如申請專利範圍第1項所述之通式(I)表示之化合物、其鹽、其N-氧化物、其溶劑化物或該等之前驅藥，係用於疼痛、搔癢症、下部尿路障害、氣喘、過敏性鼻炎、發炎性腸疾病或查加斯病之預防及/或治療。 A compound represented by the formula (I), a salt thereof, an N-oxide thereof, a solvate thereof or the like, as described in claim 1 of the patent application, for use in pain, pruritus, lower urinary tract Prevention and/or treatment of disorders, asthma, allergic rhinitis, inflammatory bowel disease or Chagas disease. 一種Trk阻害方法，其係於病患投予有效量之如申請專利範圍第1項所述之通式(I)表示之化合物、其鹽、其N-氧化物、其溶劑化物或該等之前驅藥。 A method for inhibiting Trk, which is administered to a patient by administering an effective amount of a compound represented by the formula (I), a salt thereof, an N-oxide thereof, a solvate thereof or the like as described in claim 1 of the patent application. 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